Abstract:
A pressure sensitive valve comprising: (a) an outer balloon adapted for intravascular insertion comprising at least one hole adapted for ejection of a fluid; (b) an inner structure adapted to substantially fill the outer balloon; (c) at least one selectively blockable flow path between the outer balloon and the inner structure, at least some of the at least one flow path in fluid communication with at least one of the at least one hole; (d) an inlet port to the at least one flow path; and (e) a pressure source operable to provide a fluid at least at a selected injection pressure to the inlet port. A flow of the fluid along the at least one selectively blockable flow path to the at least one hole is prevented when the pressure source provides any pressure below the selected injection pressure and a flow of the fluid along the at least one selectively blockable low path to the at least one hole occurs when the pressure source provides pressure at or above the selected injection pressure.

Description:
RELATED APPLICATIONS 
       [0001]    This application is related to U.S. Application 2006/0190022 entitled “Transvascular Ablation System” and filed on Jan. 19, 2006 and to PCT application WO 2006/006169 filed Jul. 14, 2005 and entitled “Material Delivery System”. The disclosures of these applications are each fully incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to apparatus and methods for fluid delivery. 
       BACKGROUND OF THE INVENTION 
       [0003]    A common treatment for stenosis is PTCA in which a balloon is inflated to compress the blockage and/or forcefully expand the artery. Restenosis and arterial collapse are common problems with this approach. 
         [0004]    It has been previously suggested to inject various types of medication into the site of a stenosis at high velocity. However, there are not currently any known commercially available devices which take advantage of the high injection velocity strategy. 
         [0005]    U.S. Pat. No. 5,611,775, the disclosure of which is incorporated herein by reference, describes prevention of restenosis and/or arterial collapse by injecting drugs into the blood vessel wall using a balloon with small holes deployed at the site of stenosis. Specifically, this patent describes inflating an inner balloon to force the drug through holes in an outer balloon. 
         [0006]    U.S. Pat. No. 5,614,502 entitled “High pressure impulse transient drug delivery for the treatment of proliferative diseases” and U.S. Pat. No. 6,716,190 entitled “Device and method for the delivery and injection of therapeutic and diagnostic agents to a target site within a body”, the contents of which are incorporated herein by reference, describe methods of material delivery inside the body, including transvascularly. 
         [0007]    W. J. Walker, I. M. Faireley “A simplified technique for the per catheter delivery of Isobutyl 2—Cyanoacrylate in the Embolisation of Bleeding Vessels”, Journal of Interventional Radiology 1987 2, 59-63, the contents of which is incorporated herein by reference, describes the injection of glue into a lumen and against walls of an artery, in order to block it. 
         [0008]    U.S. Pat. No. 6,280,414, the disclosure of which is incorporated herein by reference describes a tube system for delivering a drug to the wall of a blood vessel. 
         [0009]    U.S. Pat. Nos. 5,730,723 and 5,704,911, the disclosures of which are fully incorporated herein by reference, describe needleless injection apparatus. 
       SUMMARY OF THE INVENTION 
       [0010]    A broad aspect of some embodiments of the invention relates to delivery of a fluid at a high velocity into tissue surrounding an intrabody lumen. In an exemplary embodiment of the invention, the intrabody lumen is a blood vessel, optionally a coronary blood vessel. 
         [0011]    An aspect of some embodiments of the invention relates to a pressure sensitive valve which includes a valve lumen that expands to accommodate a fluid delivered at a sufficient pressure. The valve opens at, or above, the sufficient pressure to allow the delivered fluid to escape through one or more holes in a wall of the valve lumen. The sufficient pressure is referred to herein as “P injection” (P inj ). P inj  is a minimum value and injection continues as long as pressure in the valve lumen remains at or above P inj . In an exemplary embodiment of the invention, P inj  is an adjustable parameter. Optionally, adjustment can be integral in valve design or user configurable during valve use. In an exemplary embodiment of the invention, one or more of valve volume and an elasticity coefficient “K” of the wall of the valve lumen contribute to P inj . Optionally, K can be constant or variable. In an exemplary embodiment of the invention, the valve lumen is elastic only at a certain range of volumes or shape/volume combinations. 
         [0012]    In an exemplary embodiment of the invention, a volume of the lumen at pressures below P inj  is substantially zero. Optionally, a portion of the valve lumen is occupied by an inner structure. In an exemplary embodiment of the invention, the inner structure is a balloon. Optionally, the inner balloon is inflated to occupy substantially all of the lumen. In an exemplary embodiment of the invention, the inner balloon is inflated to a loading pressure which would cause it to burst if it were not supported externally by the wall of the valve lumen. 
         [0013]    In some exemplary embodiments of the invention, the valve lumen comprises an outer balloon which substantially conforms to the inner structure. Optionally, the inner structure is a balloon which causes the conformation when inflated or an inelastic structure with a fixed volume. In an exemplary embodiment of the invention, conformation of the outer balloon to the inner structure covers the hole(s) directly. In an exemplary embodiment of the invention, valves of this general configuration are re-usable. 
         [0014]    In an exemplary embodiment of the invention, the valve comprises an outer balloon which defines the valve lumen and is perforated by one or more holes and also comprises an inner structure occupying a portion of the valve lumen defined by the outer balloon. Optionally, the inner structure is an inner balloon which is inflatable independently of the outer balloon or a rigid structure with a fixed volume. According to these exemplary embodiments, the inner structure blocks a flow of fluid through the lumen of the outer balloon to the hole(s) at pressures below P inj . In an exemplary embodiment of the invention, there is a potential advantage to inflating an inner structure comprising a balloon to insure contact of the outer balloon with an external tissue (e.g. a blood vessel). 
         [0015]    In exemplary embodiments of the invention which comprise an outer balloon and an inner balloon, each of the balloons is independently characterized by a coefficient of elasticity “K”. In an exemplary embodiment of the invention, as the inner balloon is inflated, pressure in the inner balloon overcomes the K of the inner balloon and the inner balloon expands. As the inner balloon expands it overcomes the K of the outer balloon. At this stage, both balloons are inflated and substantially all of the volume of a lumen of the outer balloon is occupied by the inner balloon. In this way, the inner balloon serves to “pre-load” the outer balloon with a pressure while keeping holes in the outer balloon sealed. In an exemplary embodiment of the invention, K of the outer balloon is 500, 600, 700, 800, 900 or 1000 N/mm of additional diameter or lesser or intermediate or greater values. In an exemplary embodiment of the invention, K of the outer balloon is greater than K of the inner balloon by a factor of 2, 3, 5, or 10 or lesser or intermediate or greater values. 
         [0016]    In an exemplary embodiment of the invention, P inj  is equal to a pre-loading pressure of the inner balloon minus (K of the inner balloon times a constant). 
         [0017]    In some exemplary embodiment of the invention, the lumen of the outer structure is provided as one or more channels. Optionally, the channels can be produced in a variety of ways. One exemplary way to produce channels is to provide the inner and/or outer structure with ribs which contact a surface of an opposing structure and form channels which are in fluid communication with the holes of the outer structure. 
         [0018]    In an exemplary embodiment of the invention, a flow of fluid through the channels is blocked below P inj  by a separate element, as opposed to contact between the inner and outer structures. Optionally, the separate element can be configured as rupture discs, snap-valves or spring actuated valves. In an exemplary embodiment of the invention, a valve containing separate elements configured as rupture discs or snap valves are single use valves. In an exemplary embodiment of the invention, a valve containing separate elements configured as spring actuated valves can be re-usable. In an exemplary embodiment of the invention, the valve is configured as a normally closed valve in which the hole(s) are closed when pressure in the valve lumen is below P inj . 
         [0019]    An aspect of some embodiments of the invention relates to a method of delivering material to target cells surrounding an intrabody lumen. In an exemplary embodiment of the invention, the method includes positioning a pressure sensitive valve in proximity to the target cells, creating a resistance pressure in a valve lumen and supplying fluid to the valve lumen from a pressure source outside the body at sufficient pressure to overcome the resistance pressure. When the resistance pressure is overcome, fluid exits the valve at high velocity and is injected into tissue. 
         [0020]    An aspect of some embodiments of the invention relates to re-shaping a pressure pulse conveyed through a conduit from a proximal end to a distal end by providing a pressure sensitive valve at the distal end of the conduit. In an exemplary embodiment of the invention, the valve is configured as a balloon within a balloon. Optionally, a pressure pulse provided at a proximal end of the conduit spreads out as it travels through the conduit and is re-sharpened at a distal end of the conduit by the pressure sensitive valve. In an exemplary embodiment of the invention, the valve responds by opening in 5, 10, 20 or 50 milliseconds or lesser or greater or intermediate times when the pressure pulse arrive to the distal end of the conduit. Optionally, there is a trade-off between a time duration of the pressure pulse and a degree of re-shaping. 
         [0021]    An aspect of some embodiments of the invention relates to providing an acceleration path for molecules of liquid propelled by pressure of a sufficient magnitude. 
         [0022]    In an exemplary embodiment of the invention, the path includes a space between an outer balloon with one or more holes and an inner balloon which becomes available at P inj  or greater. 
         [0023]    In an exemplary embodiment of the invention, the path includes holes in an outer balloon which open at or above an injection pressure. Optionally, the holes are characterized by a different size and/or shape at an outer surface than at an inner surface of the balloon. Optionally, the path comprises substantially only the holes in the outer balloon. 
         [0024]    In an exemplary embodiment of the invention, the path becomes available because the outer balloon expands and/or the inner balloon contracts. 
         [0025]    In an exemplary embodiment of the invention, the path includes one or more elongate channels fitted with microvalves which open at P inj  or greater. In an exemplary embodiment of the invention, the acceleration path can be as short as, for example, 5, 10, 20, 50 or 100 microns and/or as long as 5, 10, 15, 20 or 25 mm long or shorter or intermediate or greater lengths. 
         [0026]    In an exemplary embodiment of the invention, fluid exits the holes with a velocity of 3, 5, 8 or 10 M/s or lesser or greater or intermediate velocities. Optionally, some fluid leaks from the valve at pressures below P inj . In an exemplary embodiment of the invention, the leaking occurs at low velocity. 
         [0027]    In an exemplary embodiment of the invention, there is provided a pressure sensitive valve, the valve comprising: 
         [0028]    (a) an outer balloon adapted for intravascular insertion comprising at least one hole adapted for ejection of a fluid; 
         [0029]    (b) an inner structure adapted to substantially fill the outer balloon; 
         [0030]    (c) at least one selectively blockable flow path between the outer balloon and the inner structure, at least some of the at least one flow path in fluid communication with at least one of the at least one hole; 
         [0031]    (d) an inlet port to the at least one flow path; and 
         [0032]    (e) a pressure source operable to provide a fluid at least at a selected injection pressure to the inlet port; 
         [0033]    wherein a flow of the fluid along the at least one selectively blockable flow path to the at least one hole is prevented when the pressure source provides any pressure below the selected injection pressure; and 
         [0034]    wherein a flow of the fluid along the at least one selectively blockable low path to the at least one hole occurs when the pressure source provides pressure at or above the selected injection pressure. 
         [0035]    Optionally, the outer balloon is elastic. 
         [0036]    Optionally, a coefficient of elasticity “K” of the outer balloon is at least 500 N/mm. 
         [0037]    Optionally, the inner structure comprises a balloon. 
         [0038]    Optionally, the balloon is elastic. 
         [0039]    Optionally, a coefficient of elasticity “K” of the outer balloon is at least 100% greater than a coefficient of elasticity of the inner balloon. 
         [0040]    Optionally, the outer balloon conforms to the inner structure at any pressure below the selected injection pressure. 
         [0041]    Optionally, the outer balloon expands when pressure at the inlet port reaches or exceeds the selected injection pressure. 
         [0042]    Optionally, the valve is provided as a portion of an atherectomy catheter. 
         [0043]    In an exemplary embodiment of the invention, there is provided a method of delivering fluid to tissue surrounding an intrabody lumen at a high velocity, the method comprising: 
         [0044]    (a) inserting a pressure sensitive valve into an intrabody lumen, the valve configured to prevent a flow of fluid from one or more holes at any pressure below a selected injection pressure and to permit the flow at the selected injection pressure or greater; and 
         [0045]    (b) delivering a fluid pulse to the valve at the selected injection pressure or greater. 
         [0046]    Optionally, the valve is adjacent to one or more holes. 
         [0047]    Optionally, the valve comprises one or more holes. 
         [0048]    Optionally, the fluid pulse comprises a liquid medication. 
         [0049]    Optionally, exit of a volume not exceeding 0.25 ml reduces pressure in the valve below the selected injection pressure. 
         [0050]    Optionally, the selected injection pressure is at least 10 atmospheres. 
         [0051]    Optionally, delivering fluid to the valve at the selected injection pressure or greater is repeated and the flow is prevented between repetitions. 
         [0052]    Optionally, the method comprises adjusting an ejection direction between repetitions. 
         [0053]    Optionally, the method comprises adjusting a position of the valve between the repetitions. 
         [0054]    Optionally, the method is performed in conjunction with a stenosis therapy procedure. 
         [0055]    Optionally, the stenosis therapy procedure comprises atherectomy. 
         [0056]    Optionally, the stenosis therapy procedure comprises PTCA. 
         [0057]    In an exemplary embodiment of the invention, there is provided a method of delivering fluid to tissue surrounding an intrabody lumen at a high velocity, the method comprising: 
         [0058]    (a) inserting a pressure sensitive valve comprising an outer balloon with one or more holes and an inner balloon into an intrabody lumen; 
         [0059]    (b) inflating the inner balloon so that it conforms to the outer balloon; and 
         [0060]    (c) causing fluid to flow into a lumen of the outer balloon at a sufficient pressure to cause at least a portion of the fluid to exit the balloon through the holes at a velocity sufficient to penetrate surrounding tissue while the inner balloon remains inflated. 
         [0061]    Optionally, (a) occurs first, (b) occurs second and (c) occurs third. 
         [0062]    Optionally, the method comprises inflating the inner balloon to open a stenosis. Optionally, the method comprises reducing pressure in the inner balloon after opening the stenosis. 
         [0063]    In an exemplary embodiment of the invention, there is provided a method of delivering fluid to tissue surrounding an intrabody lumen at a high velocity, the method comprising: 
         [0064]    (a) stopping molecules of liquid propelled by an increasing pressure approaching a selected injected pressure, the increasing pressure supplied from a pressure source outside the body, using a pressure sensitive valve installed in a body lumen; and 
         [0065]    (b) opening an acceleration path for the molecules when the increasing pressure reaches or exceeds the selected injection pressure 
         [0066]    Optionally, the valve stops the molecules within the valve. 
         [0067]    Optionally, the valve stops the molecules prior to entry into the valve. 
         [0068]    Optionally, opening the acceleration path comprises stretching an elastic membrane. 
         [0069]    Optionally, the stretching an elastic membrane comprises expanding an elastic balloon. 
         [0070]    Optionally, opening the acceleration path comprises deforming a plastically deformable element. 
         [0071]    Optionally, opening the acceleration path comprises deforming an elastically deformable element. 
         [0072]    Optionally, opening the acceleration path comprises opening one or more elongate channels by operating one or more microvalves which open at the selected injection pressure. 
         [0073]    In an exemplary embodiment of the invention, there is provided a pressure sensitive valve, the valve comprising: 
         [0074]    (a) a biocompatible unit, the unit adapted for insertion in an intrabody lumen; 
         [0075]    (b) at least one acceleration path for a fluid, each of the at least one acceleration path terminating in at least one hole facing outwards from the biocompatible unit; 
         [0076]    (c) an inlet port to the at least one flow path; 
         [0077]    (d) a pressure source operable to provide fluid at a selected injection pressure to the inlet port; and 
         [0078]    (e) at least one flow restriction element adapted to:
       (i) block a flow of the fluid along the at least one flow path at any pressure below the selected injection pressure; and   (ii) permit a flow of the fluid along the at least one flow path at the selected injection pressure or greater.       
 
         [0081]    In an exemplary embodiment of the invention, there is provided a liquid drug delivery device for treating intra-body lumen tissues, the device comprising: 
         [0082]    an inflatable inner structure containing a fluid at a substantially constant inner threshold pressure; 
         [0083]    an outer structure having at least one hole, adapted for ejecting the drug; 
         [0084]    a volume between said structures containing a liquid drug at a first pressure, which is substantially equivalent to said threshold pressure; and 
         [0085]    a pressure pulse source having direct communication with said volume, adapted to substantially increase the pressure in said volume, when activated, for a period not exceeding 100 milliseconds; 
         [0086]    wherein said inner structure seals said at least one hole when said pressure pulse source is not activated. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0087]    Exemplary non-limiting embodiments of the invention described in the following description, read with reference to the figures attached hereto. In the figures, identical and similar structures, elements or parts thereof that appear in more than one figure are generally labeled with the same or similar references in the figures in which they appear. Dimensions of components and features shown in the figures are chosen primarily for convenience and clarity of presentation and are not necessarily to scale. The attached figures are: 
           [0088]      FIGS. 1A and 1B  are flow diagrams illustrating exemplary methods according to some embodiments of the invention; 
           [0089]      FIG. 2A  is a schematic diagram of a fluid delivery system according to an exemplary embodiment of the invention; 
           [0090]      FIGS. 2B and 2D  are cross sections of exemplary catheters according to embodiments of the invention at line B-B of  FIG. 2A ; 
           [0091]      FIG. 2C  is a cross section of an exemplary catheter according to an embodiment of the invention at line A-A of  FIG. 2A ; 
           [0092]      FIGS. 3A ,  3 B,  3 C and  3 D are schematic diagrams illustrating an operational sequence of a pressure sensitive valve according to an exemplary embodiment of the invention; 
           [0093]      FIGS. 3E and 3F  are lateral and transverse cross sections respectively of a pressure sensitive valve according to another exemplary embodiment of the invention; 
           [0094]      FIGS. 4A and 4B  are schematic diagrams of a “fluid gun” according to an exemplary embodiment of the invention in “cocked” and “fired” states respectively; 
           [0095]      FIGS. 5A ,  5 B,  5 C and  5 D illustrate exemplary arrangements of holes on a balloon according to exemplary embodiments of the invention; 
           [0096]      FIG. 6  is a micrograph of tissue illustrating penetration of material injected using an apparatus according to an exemplary embodiment of the invention; 
           [0097]      FIGS. 7 and 8  are cross sectional views of additional exemplary embodiments of pressure sensitive valves according to the invention; 
           [0098]      FIG. 9  is a graph illustrating internal pressure profiles of an inner balloon (dotted line) and outer balloon (solid line) during an exemplary injection event according to one embodiment of the invention; and 
           [0099]      FIGS. 10A and 10B  are diagrams illustrating operation of opposing forces in valves according to exemplary embodiments of the invention. 
       
    
    
     DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       [0100]    Overview 
         [0101]      FIG. 1A  is a simplified flow diagram illustrating an exemplary method of injecting a therapeutic agent into tissue surrounding an intrabody lumen. 
         [0102]      FIG. 2A  is a schematic diagram of an exemplary system  200  configured to perform exemplary method  100 . System  200  is depicted as including a pressure sensitive valve  300  which is depicted in greater detail in  FIGS. 3A ,  3 B,  3 C and  3 D which are described below. Exemplary valve  300  is a double chambered device characterized by an inner chamber and an outer chamber. Other components of system  200  serve to independently regulate internal pressures of the inner and outer chambers. 
         [0103]    In other exemplary embodiments of system  200 , valve  300  is replaced by a valve with a different configuration. Exemplary alternate valve configurations  302  and  304  are depicted in  FIGS. 3E-3F ,  7  and  8  respectively and will be described below. According to various exemplary embodiments of the invention, the pressure sensitive valve is configured according to the specific application for which it is designed. 
         [0104]    Referring now to  FIGS. 1A and 2A  operation of exemplary valve  300  is explained: 
         [0105]    At  102  a pressure sensitive valve  300  is provided in a body of a subject. Optionally, provision  102  is by insertion along a guidewire  260 . In an exemplary embodiment of the invention, an inner balloon  270  (see also  FIG. 7 ) or  870  ( FIG. 8 ), is inflated to a desired volume at a desired pressure, for example using a pump  210 . 
         [0106]      FIG. 1B  describes the act of providing  102  in greater detail and will be explained below. 
         [0107]    At  104  a pressure pulse is directed to valve  300  from a pressure source outside body, for example a pressure pulse “gun”  214 . 
         [0108]    The pressure pulse causes pressure in valve  300  to reach a desired injection pressure (P inj ) and open  106 . It is stressed that P inj  can vary with a coefficient of elasticity “K” and/or a volume of one or more parts of valve  300  as will be explained below. As long as pressure within valve  300  remains at P inj  or greater, fluid is expelled at a high velocity and valve  300  remains open  106 . 
         [0109]    In an exemplary embodiment of the invention, valve  300  maintains  108  an internal pressure of at least P inj  until a sufficient volume of fluid has been ejected. 
         [0110]    As fluid is ejected from valve  300 , pressure in valve  300  drops  110  below P inj  and valve  300  closes  112 . A tendency of pressure in valve  300  to drop below P inj  can be at least partially mitigated by supply of additional fluid to the valve at P inj  or greater. 
         [0111]    In the described embodiment, valve  300  is not damaged by being opened so that it can be opened  106  and closed  112  many times. In an exemplary embodiment of the invention, valve  300  can be reused. Optionally, re-use occurs at a same location or at a different location. 
         [0112]    Depicted exemplary valve  300  comprises a pair of balloons (e.g.  270  and  280 ) nested one within the other. 
         [0113]    In an exemplary embodiment of the invention, inner balloon  270  and outer balloon  280  are both elastic. Optionally, P inj  according to this embodiment of valve  300  is governed at least in part by an inflation volume of inner balloon  270  and/or by an inflation pressure of inner balloon  270  and/or by K of outer balloon  280  at that volume. 
         [0114]    In an exemplary embodiment of the invention, inner balloon  270  is elastic and outer balloon  280  is inelastic. Optionally, P inj  according to this embodiment of the invention is governed at least in part by an available compliance volume of inner balloon  270 . Compliance volume of inner balloon  270  may be affected by one or more of a compressibility of a material used to fill the balloon, an ability of a conduit connected to balloon  270  to accommodate fluid exiting the balloon, a compliant element in fluid communication with fluid in the system, a degree of compliance of pump  210  and a direction of flow of pump  210  at a relevant time. 
         [0115]    In an exemplary embodiment of the invention, inner balloon  270  is inelastic but compliant and outer balloon  280  is elastic. Optionally, P inj  according to this embodiment of valve  300  is governed at least in part by one or more of an inflation volume of inner balloon  270 , by K of outer balloon  280  at that volume and by an available compliance volume of inner balloon  270  as described above. 
         [0116]    According to various exemplary embodiments of the invention, medication injected from valve  300  reduces a likelihood of restenosis after a PTCA procedure and/or alters structural and/or electrical properties of tissue and/or delivers a therapeutic and/or cyto-toxic agent. 
         [0117]    Referring now to  FIGS. 1B and 2A , the act of providing  102  of valve  300  according to some exemplary embodiments of the invention is explained in greater detail. 
         [0118]    In an exemplary embodiment of the invention, a medical procedure begins with insertion  118  of valve  300  comprising outer balloon  280  and inner balloon  270  into blood vessel  310  (see  FIG. 3A ). Optionally, insertion is along a guidewire  260 . In an exemplary embodiment of the invention, valve  300  is used to perform a PTCA as well as to inject fluid so the insertion is to a site of stenosis  320 . 
         [0119]    After insertion  118  to a desired site, inner balloon  270  is inflated  120 . If PTCA is to be performed, inflation can be to a PTCA pressure. A PTCA pressure is typically in excess of 5, 10, 20 or 30 atmospheres. In an exemplary embodiment of the invention, pressure for inflation is provided by a pump  210  which pumps fluid via tubing  216  and/or connector  220  to lumen  254  of catheter  250  which is in fluid communication with lumen  272  of inner balloon  270 . In an exemplary embodiment of the invention, pressure supplied by pump  210  is monitored, for example by a gauge on pump  210  and/or by a pressure sensor in balloon  270 . Optionally, initial inflation can be to a PTCA pressure and pressure can be reduced for subsequent operation of valve  300  as an injector. 
         [0120]    In an exemplary embodiment of the invention, inner balloon  270  expands and contacts an inner surface of outer balloon  280  sealing  130  holes  290 . Optionally, balloon  270  is expanded to a degree which concurrently opens holes  290  (e.g. by stretching) and seals holes  290  (e.g. by covering). In the embodiment depicted in  FIG. 3B , balloon  270  is shown contacting holes  290 . In other exemplary embodiments of the invention, balloon  270  prevents a flow of fluid to holes  290  by contacting portions of balloon  280  other than holes  290  (e.g. a ring at the neck of the balloon). Valve  300  is now in a closed operational state. If an optional PTCA is being performed, expansion of inner balloon  270  causes outer balloon  280  to expand  132  and open vessel  310 . 
         [0121]    In an exemplary embodiment of the invention, while valve  300  is closed, pump  212  delivers  140  liquid medication via lumen  256  of catheter  250  to an entrance to inner lumen  282  of outer balloon  280  at a pressure slightly P inj . Optionally, lumens  256  and/or  282  are pre-filled (e.g. with medication) prior to insertion  118 . In an exemplary embodiment of the invention, pre-filling removes trapped air. 
         [0122]    At this stage, inner balloon  270  continues  160  to seal holes  290  of outer balloon  280  so that valve  300  remains closed. 
         [0123]    In order to cause valve  300  to open, a pulse gun  214  applies  170  a pressure pulse via lumen  256  so that pressure at the entrance to inner lumen  282  of outer balloon  280  increases to at least P inj . This increase causes fluid to flow into inner lumen  282  of outer balloon  280  at P inj . The pressure in lumen  282  of balloon  280  causes inner balloon  270  and outer balloon  280  to separate  180 . Separation can result from contraction of inner balloon  270  (if it is sufficiently compliant)  180  and/or expansion of outer balloon  280  (if it is sufficiently elastic). In the depicted exemplary embodiment of the invention ( FIG. 3D ), contraction  180  of inner balloon  270  uncovers  182  at least some of holes  290  of outer balloon  280 . Medication exits  184  via uncovered holes  290  at P inj  or greater. In various exemplary embodiments of the invention, a degree to which an actual pressure driving exit  184  exceeds P inj  can vary with a magnitude of the pressure pulse delivered by gun  214  and/or characteristics of catheter  250 . Because the medication is driven by a relatively high pressure, it penetrates into tissue of blood vessel  310 . The P inj  at which valve  300  opens is optionally chosen according to a desired penetration profile of the medication. 
         [0124]      FIGS. 3A to 3D ,  3 E to  3 F and  7  and  8  illustrate exemplary pressure sensitive valves according to various exemplary embodiments of the invention which operate as described above and can be used in conjunction with a system as depicted in  FIG. 2A . 
       Operation of an Exemplary Pressure Sensitive Valve 
       [0125]      FIGS. 3A ,  3 B,  3 C and  3 D illustrate operation of an exemplary nested balloon valve  300  graphically. Each of these figures is a lateral cross section of valve  300  showing a catheter  250 , an optional guidewire  260 , an inner structure  270  and an outer structure  280  with at least one hole  290  (a plurality of holes  290  are pictured) in a blood vessel  310 , or other intrabody lumen. Optionally, pictured catheter  250  can be replaced by analogous fluid supply conduits. In the depicted valve  300 , the outer structure comprising holes  290  is outer balloon  280  and the inner structure is inner balloon  270 . 
         [0126]    In this series of drawings a “rapid exchange” embodiment of catheter  250  is depicted. In the pictured embodiment, guidewire  260  is outside catheter  250  proximal to rapid exchange hole  262 . 
         [0127]    In other exemplary embodiments of the invention, catheter  250  is an “over the wire” catheter. 
         [0128]    In other exemplary embodiments of the invention, catheter  250  is deployed without a guidewire. Deployment without a guidewire may be suitable, for example, in non-vascular applications. Non-vascular applications may include, for example, prostate treatment, urinary bladder treatment, rectal treatment, intranasal treatment, vaginal treatment and uterine treatment. 
         [0129]    In  FIG. 3A  valve  300  is shown positioned in proximity to a stenosis  320  just prior to a PTCA procedure. This positioning of valve  300  is exemplary only. 
         [0130]      FIG. 3B  illustrates performance of PTCA using pump  210  ( FIG. 2 ) to inject fluid via lumen  254  of catheter  250  into lumen  272  of inner balloon  270  (indicated by curved arrows) causing inner balloon  270  to expand  130 . Expansion  130  pushes stenosis  320  outwards and opens blood vessel  310 . Expansion  130  of inner balloon  270  closes holes  290  and brings them into close proximity with inner walls of vessel  310 . Expansion  130  brings valve  300  to a closed operational state. In an exemplary embodiment of the invention, pump  210  inflates inner balloon  270  with a standard PTCA pressure, for example 5, 10, 12, 15, 17 or 20 atmospheres or intermediate or greater pressures. These pressures are generally sufficient to expand stenosis  320 . Optionally, the pressure applied for PTCA contributes to defining P inj  for operation of valve  300 . Optionally, pressure in inner balloon  270  is adjusted after the PTCA procedure. 
         [0131]    In an exemplary embodiment of the invention, P inj  is defined by the following formula: 
         [0000]    
       
      
       P 
       inj 
       =P 
       internal 
       −[K 
       i 
       −X] 
      
     
         [0132]    Where: P internal  is an inflation pressure of the inner balloon;
       K i  is a coefficient of elasticity of the inner balloon an   X is a constant.       
 
         [0135]    The lower portion of  FIG. 3B  indicates a cross section of catheter  250  at three different (indicated) positions. These cross sections indicate how different lumens of catheter  250  can deliver fluid in an independently controllable manner to lumen  272  of inner balloon  270  and lumen  282  of outer balloon  280  and provide a conduit for guidewire  260  to pass through both balloons. 
         [0136]    The left-most cross-section illustrates three lumens which characterize exemplary catheter  250  until it passes within inner lumen  282  of outer balloon  280 . The three lumens are: an inner balloon catheter lumen  254 , a guidewire catheter lumen  258  and an outer balloon catheter lumen  256 . Outer balloon catheter lumen  256  ends in lumen  282  of outer balloon  280  where it delivers fluid. Valve  300  switches from a closed to an open state when fluid delivery via outer balloon catheter lumen  256  reaches P inj . 
         [0137]    In an exemplary embodiment of the invention, outer balloon lumen  256  is ellipsoid, optionally elliptical, in cross section. A non-circular cross-sectional area of outer balloon lumen  256  contributes to a greater capacity to conduct a high pressure fluid pulse from pulse gun  214  to inner lumen  282  of outer balloon  280  by contributing to an increased fluid flow without changing an outer diameter of catheter  250 . 
         [0138]    In an exemplary embodiment of the invention, outer balloon lumen  256  is elliptical and has a major axis of 0.6 mm and a minor axis of 0.43 mm. This exemplary configuration for lumen  256  provides a cross-sectional area of 0.22 mm 2 . In an exemplary embodiment of the invention, guidewire lumen  258  is characterized by an inner diameter of 0.38 mm and inner balloon lumen  254  is characterized by an inner diameter of 0.2 to 0.33 mm. This exemplary configuration permits the three lumens to be provided in a standard PTCA catheter with an outer diameter of 1.1 mm. 
         [0139]      FIG. 2D  shows another exemplary embodiment of outer balloon lumen  256  in a cross section at B-B. According to the depicted embodiment, outer balloon lumen  256  occupies a majority of the cross sectional area of catheter  250 . Optionally, lumen  256  is at least partially concave in cross section. In an exemplary embodiment of the invention, having outer balloon lumen  256  occupy a majority of the cross sectional area of catheter  250  contributes to efficiency of conducting a pressure pulse from gun  214  to inner lumen  282  of outer balloon  280 . Optionally, the contribution to efficiency of conducting a pressure pulse results from reduced friction of fluid against walls of lumen  256 . Optionally, the contribution to efficiency of conducting a pressure pulse results from increased velocity of fluid within lumen  256 . According to the depicted exemplary embodiment, lumen  256  is characterized by a cross-sectional area of 0.40 mm 2  and still fits within a standard PTCA catheter. 
         [0140]    The middle cross-section in  FIG. 3B  illustrates two lumens which characterize exemplary catheter  250  within at least a portion of inner lumen  272  of inner balloon  270 . The two lumens are: inner balloon lumen  254  and guidewire lumen  258 . In  FIG. 3B  these two lumens are illustrated as being side by side in this portion of catheter  250 . In another exemplary embodiment of the invention, these two lumens ( 258  and  254 ) are nested one within the other. Inner balloon lumen  254  ends in lumen  272  of inner balloon  270  where it delivers fluid to inflate inner balloon  270 . 
         [0141]    The right-most cross-section illustrates a single guide wire lumen  258  which characterizes exemplary catheter  250  from within inner lumen  272  of inner balloon  270  until a distal end of catheter  250 . 
         [0142]      FIG. 3C  illustrates pumping  140  of medication into inner lumen  282  of outer balloon  280  at a pressure below P inj . Lumen  282  is external with respect to inner balloon  270 . At this stage of operation of valve  300 , medication is optionally pumped  140  by outer balloon pump  212  which can be, for example, a conventional PTCA pump. In an exemplary embodiment of the invention, pumps  212  and  210  are similar, optionally identical. In an exemplary embodiment of the invention, each of pumps  212  and  210  is equipped with a pressure gauge so that a user can deliver a desired pressure. Pump  212  pumps  140  medication into lumen  282  at a pressure below P inj  (indicated by arrows emanating from lumen  256 ). The degree to which pressure delivered by pump  212  at this stage is below P inj  can vary with an anticipated magnitude of a pressure pulse to be delivered later. Holes  290  remain closed by pressure in lumen  272  of inner balloon  270  at this stage. 
         [0143]    Optionally, connector  220  is adjusted at this stage so that pulse gun  214  is connected to lumen  256  in place of pump  212 . Adjustment may involve, for example, rotating a control lever of a stopcock or disconnecting pump  212  and connecting gun  214  in place thereof. 
         [0144]    In an exemplary embodiment of the invention, both pump  212  and gun  214  are connected to lumen  256  concurrently. In an exemplary embodiment of the invention, an output from gun  214  enters lumen  256  downstream of an output from pump  212 . 
         [0145]      FIG. 3D  shows delivery of a pulse of pressure (represented as arrows) from pulse gun  212  via lumen  256  of catheter  250  into lumen  282  of outer balloon  280 . Delivery of the pulse raises pressure  170  in lumen  282  at least to P inj , optionally to a pressure well in excess of P inj  As soon as pressure in lumen  282  reaches P inj  (e.g. by exceeding T), holes  290  are uncovered  182  and medication exits holes  290  at high velocity. 
         [0146]    In the depicted embodiment, holes  290  may become uncovered  182  because inner balloon  270  contracts and/or because outer balloon  280  expands. The extent to which inner balloon  270  contracts and/or outer balloon  270  expands may be influenced by one or more of elasticity of inner balloon  270 , elasticity of outer balloon  280 , a magnitude of a difference between pressure in lumen  272  of inner balloon  270  and P inj , opposing forces applied by vessel  310 , compliance of lumen  256 , compliance of gun  214  and compliance of pump  212 . 
         [0147]    In an exemplary embodiment of the invention, pressure in lumen  272  of inner balloon  270  is optionally 8, 10, 12, 14 or 16 atmospheres or lesser or greater or intermediate pressures, which is typically sufficient to open a stenosis. 
         [0148]    In an exemplary embodiment of the invention, a pressure pulse wave of 100 to 280 atmospheres exiting pulse gun  214  produces an initial velocity of fluid in lumen  256  of 20, 50, 75 or 100 meters/second or lesser or intermediate or greater values. A pulse wave of this magnitude exiting gun  214  provides at least P inj  in lumen  282  of valve  300  and switches the valve from closed to open. 
         [0149]    A magnitude of the pulse delivered by gun  214  can be controlled by manipulating force applied by an actuation mechanism (e.g. gas pressure or spring resistance) in gun  214 . 
         [0150]    As the pulse wave moves through lumen  256  of catheter  250 , the pressure pulse wave is reduced in amplitude. A degree of amplitude damping can vary with length and/or cross-sectional area of lumen  256  and materials employed in catheter construction. 
         [0151]    When a leading edge of the wave reaches lumen  282  of outer balloon  280 , pressure in lumen  272  of inner balloon  270  tends to prevent the leading edge of the pressure wave from proceeding further. As more of the wave arrives, pressure to enter lumen  282  increases. In an exemplary embodiment of the invention, when the pressure reaches P inj  minus 2 atmospheres, fluid begins to enter lumen  282 . A pressure at which fluid begins to enter lumen  282  may vary with one or more pressure in lumen  272  of inner balloon  270 , elastic properties of outer balloon  280  and a counter-expansive force applied to balloon  280  by vessel  310 . When pressure in lumen  282  reaches P inj  holes  290  open and fluid is ejected at high velocity. In an exemplary embodiment of the invention fluid is ejected from valve  300  at 14, optionally 20, optionally 30, optionally 34, optionally 40 atmospheres or intermediate or greater values. In an exemplary embodiment of the invention fluid is ejected from valve  300  at an average velocity greater than 10, optionally 20, optionally 50, optionally 100, optionally 200 m/s. In some preferred embodiments of the invention, increasing ejection velocity and/or injection pressure contributes to a greater depth of penetration and/or a shorter injection time. 
         [0152]    Optionally, the pressure wave continues to arrive in lumen  282  after holes  290  open. In an exemplary embodiment of the invention, actual pressure in lumen  282  during an injection event exceeds pressure in lumen  272  of inner balloon  270  by 2, optionally 4, optionally 8, optionally 16, optionally 24 atmospheres or intermediate or greater pressure differentials. 
         [0153]    In an exemplary embodiment of the invention, a degree by which P inj  must exceed pressure in lumen  272  of inner balloon  270  and/or an actual pressure desired in lumen  282  during an injection event is considered when planning a pressure pulse to deliver fluids. If P inj  and/or an actual pressure in lumen  282  during an injection event exceeds pressure in lumen  272  of inner balloon  270  by too much, an exit velocity of fluid from holes  290  can be excessive. Excessive exit velocity can potentially cause tissue damage and/or cause delivery of fluid to an incorrect tissue layer and/or damage outer balloon  280  and/or inner balloon  270 . 
         [0154]    Optionally, ejection of fluid from holes  290  lasts 5, 10, 20, 50, 75 or 100 milliseconds or lesser or intermediate or greater times. During this ejection time, pressure in lumen  282  remains at least at P inj , and may optionally be much higher. Optionally, a degree by which pressure in lumen  282  of valve  300  differs from pressure in lumen  272  of inner balloon  270  can remain constant or vary during this time interval. In an exemplary embodiment of the invention, the degree by which pressure in lumen  282  of valve  300  differs from pressure in lumen  272  of inner balloon  270  increases and then decreases during this time until pressure in lumen  282  falls below P inj . Delivery of the pressure wave is described in greater detail below in a section entitled “Pulse Wave Delivery”. 
         [0155]    Optionally, pump  212  and gun  214  are incorporated into a single apparatus. 
         [0156]    When valve  300  opens as a result of an applied pressure pulse, exit  184  of medication causes pressure in lumen  282  of outer balloon  280  to return  190  to drop below P inj  so that inner balloon  270  covers holes  290  closing valve  300 . 
         [0157]    Optionally, this sequence of opening/closing valve  300  can be repeated cyclically at a same location or a series of different locations. According to various exemplary embodiments of the invention, valve  300  can deliver multiple doses of medication to a single site (e.g. stenosis site) by application of multiple pressure pulses from gun  214 . Alternatively or additionally, valve  300  can deliver medication to multiple sites if it is navigated to additional sites between pressure pulses from gun  214 . 
         [0158]    In other exemplary embodiments of the invention a pressure of at least P inj  is applied as a constant pressure (as opposed to a pulse) and valve  300  remains open until application of the pressure ceases. 
         [0159]    In an exemplary embodiment of the invention, operation of valve  300  causes ejection of medication from at least 50, 60, 70, 80, 85, 90, 95 or substantially 100% of holes  290 . 
       Additional Exemplary Valve Configurations 
       [0160]      FIGS. 7 and 8  are cross sectional drawings of additional exemplary valve configurations  302  and  304  respectively according to embodiments of the invention. 
         [0161]      FIG. 7  illustrates a non-cylindrical valve  302  with deflated inner balloon  270 D (solid line) and inflated inner balloon  270 I (dotted lines). As described above with reference to  FIGS. 3A ,  3 B,  3 C and  3 D, introducing liquid or gas via lumen  254  of catheter  250  into inner lumen  272  of balloon  270  inflates inner balloon  270  so that it expands and inflates outer balloon  280 . Holes  290  in outer balloon  280  are covered by inner balloon  270 . 
         [0162]    Subsequent introduction of medication via lumen  256  of catheter  250  to inner lumen  282  of outer balloon  280  creates a separative force between the two balloons. In an exemplary embodiment of the invention, delivery of a pressure pulse via lumen  256  of catheter  250  causes the separative force to reach and/or exceed P inj . 
         [0163]    When P inj  is reached or exceeded, balloons  270  and  280  separate and medication flows through lumen  282  and outward from holes  290 . Holes  290  are pictured in  FIG. 7  as being distributed throughout the surface of outer balloon  280 . This exemplary arrangement of holes produces radial ejection of fluid with respect to balloon  280 . 
         [0164]    However, in other exemplary embodiments of valves according to the invention, holes  290  may be concentrated in a particular area of balloon  280  to achieve ejection of medication in a desired direction. 
         [0165]    Non-cylindrical valves  302  may optionally be useful in non-tubular lumens. Non-tubular lumens include nostrils and nasal sinuses. 
         [0166]      FIG. 8  illustrates a valve  304  with an outer structure  880  constructed of an inelastic material, optionally with a shape memory. In the depicted embodiment, a single hole  290  is pictured. In  FIG. 8 , inner balloon  870  is shown only partially inflated so that hole  290  is unblocked and valve  304  is open. 
         [0167]    In other exemplary embodiments of the invention, multiple holes  290  are provided on outer structure  880 . In an exemplary embodiment of the invention, placement of hole or holes  290  is used to choose one or more ejection directions. Optionally, one or more markers  850  (e.g. radio-opaque markers) are provided on outer structure  880 . In an exemplary embodiment of the invention, markers  850  and a surface  810  of a target tissue  800  are visualized by medical imaging (e.g. X-ray or fluoroscopy). Optionally, outer structure  880  can be rotated or otherwise adjusted to bring markers  850  into a desired orientation with respect to target tissue  800  so that ejection of medication from hole(s)  290  will be into a desired location on surface  810  of target tissue  800 . Ejection of fluid is accomplished by delivery of a pressure pulse to achieve P inj  or greater as described above. 
         [0168]    In an exemplary embodiment of the invention, valve  304  is used to deliver a single high speed jet of fluid to a specific sight inside the body, optionally from a single hole  290 . 
         [0169]    Referring again to  FIG. 3D , in some exemplary embodiments of the invention only one balloon is employed to form valve  300 . Optionally, an elastic outer balloon  280  with holes  290  is filled with an inelastic form  270  of sufficient strength to resist deformation at P inj  or other pressures in lumen  282  which may result from delivery of a pressure pulse as described above. Operation of this exemplary valve  300  is similar to that described above except that P inj  is used to overcome elastic contraction of outer balloon  280  against inelastic form  270 . Optionally, inelastic form  270  is provided as a solid body. A coefficient of elasticity K of outer balloon  280  at a volume defined by inner structure  270  substantially governs P inj  according to this embodiment of the invention. Briefly, delivery of PP from gun  214  causes pressure in lumen  282  of outer balloon  280  to reach and/or exceed P inj . Inelastic form  270  does not contract at P inj . According to this exemplary embodiment, shape and/or volume of inner structure  270  contribute to P inj . Outer balloon  280  expands, opening holes  290  and permitting ejection of fluid therefrom. This type of valve configuration can be useful in applications where an outer diameter of valve  300  is not a limit for providing  102  and/or insertion  118 . 
         [0170]      FIGS. 3E and 3F  depict another exemplary valve configuration  310  in lateral cross section ( FIG. 3E ) and transverse cross section at line C-C ( FIG. 3F ). In valve  310 , inner structure  270 , depicted as a balloon  270  with a lumen  272 , is provided with ribs  370  on its external surface. Ribs  370  contact outer balloon  280  and divide lumen  282  into a plurality of flow channels  382 . According to this exemplary embodiment of the invention, a flow of fluid into channels  382  is blocked below P inj  by one or more microvalves  390  which are each individually set to open at P inj . Microvalves  390  can be provide as rupture discs, snap-valves or spring actuated valves. Valves  310  containing microvalves  390  configured as rupture discs or snap valves are single use valves. Valves  310  containing microvalves  390  configured as spring actuated valves can be re-usable. In an exemplary embodiment of the invention, when microvalves  390  open at P inj , fluid rushes into channels  382  of lumen  282  of outer balloon  280  and accelerates towards and through holes  290 . 
         [0171]    In an exemplary embodiment of the invention, the configuration depicted in  FIG. 3E  can be applied to a solid inner body  270  at least partially covered by an outer membrane  280  to define channels  282 . 
         [0172]    Exemplary Hole Geometries 
         [0173]      FIGS. 5A ,  5 B,  5 C and  5 D illustrate exemplary patterns of holes  290  on outer balloon  280 . In all of these figures, balloon  280 , which is typically cylindrical or ovoid is depicted in a cut plan view. Vertical rows of holes  290  represent circumferential rings about balloon  280 . Flow of medication under pressure into lumen  282  is from left to right in all  4  drawings as indicated by the arrow in  FIG. 5A . Holes  290  are optionally round or elliptical or slits. 
         [0174]    In an exemplary embodiment of the invention, round holes  290  have a diameter of 10, 20, 30 or 40 microns or lesser or intermediate or greater diameters. Optionally, as dimensions of a hole  290  increase, an ability of the hole to dissipate pressure increases. However, if holes  290  are too large (e.g. diameter of 50 μm more in), injection may occur only through those holes  290  located in a proximal portion of balloon  280 . Conversely, if holes  290  are too small (e.g. diameter of 1-5 μm) the desired high velocity ejection of fluid may be replaced by sweating or dripping of fluid from balloon  280 . 
         [0175]      FIG. 5A  depicts an exemplary embodiment in which holes  290  are arranged in equally spaced vertical rows. Optionally, distance between holes  290  in a row is equivalent. This exemplary arrangement allows pressure in lumen  282  to decrease as the pressure wave moves from left to right because each additional row of holes releases pressure from lumen  282 . In some exemplary embodiments of the invention, a non-constant pressure in lumen  282  is not desired. 
         [0176]      FIG. 5B  depicts an exemplary embodiment in which holes  290  are arranged in vertical rows with a decreasing distance between each successive row. Optionally, distance between holes in a row is equivalent. This configuration is designed to contribute to equalization of an amount of medication delivered per unit length of balloon  280  by providing additional holes in a distal portion of balloon  280  where pressure in lumen  282  is lower. Optionally, penetration depth is lower in a distal portion of balloon  280  in this configuration. 
         [0177]      FIG. 5C  depicts an exemplary embodiment in which holes  290  are arranged in vertical rows with an increasing number of holes per row. Optionally, distance between rows is equivalent. This configuration is designed to contribute to equalization of an amount of medication delivered per unit length of balloon  280 . Optionally, equalization is achieved by reducing a degree by which pressure in lumen  282  is lowered in a proximal portion of balloon  280 . 
         [0178]      FIG. 5D  depicts an exemplary embodiment in which proximal holes  290  are of a smaller size and distal holes  292  are of a larger size. Optionally, distance between vertical rows is equivalent. Optionally, distance between holes within a row is equivalent. This configuration is designed to contribute to equalization of an amount of medication delivered per unit length of balloon  280  by providing additional cross sectional area of holes in a distal portion of balloon  280  where a difference between T and pressure in lumen  282  is lower. 
         [0179]    In another exemplary embodiment of the invention (not pictured) a diameter of holes  290  increases incrementally and distally along an axis of balloon  280 . This exemplary embodiment is designed to contribute to equalization of an amount of medication delivered per unit length of balloon  280  as for the embodiments depicted in  FIGS. 5B ,  5 C and  5 D. Embodiments of this type can offer an advantage in manufacturing as production of a relatively small number of larger holes with larger intervening spaces may be less difficult than production of a relatively large number of smaller holes with smaller intervening spaces. 
         [0180]    The exemplary embodiments depicted in  FIGS. 5A ,  5 B,  5 C and  5 D are all designed to provide radially symmetric ejection of medication with respect to a long axis of outer balloon  280 . However, in some exemplary embodiments of the injection, non-radially symmetric ejection is provided. Non radially symmetric ejection may be achieved, for example, by providing holes  290  and/or  292  only on a desired angular range of balloon  280  with respect to its long axis. For example, holes  290  and/or  292  can be provided on 180, 120, 90, 60, 45 or 30 degree circumferential arcs of balloon  280  or lesser or intermediate or greater circumferential arcs of balloon  280 . Non-radially symmetric hole configurations may be useful in treating lumen abnormalities which occur only on a selected portion of a lumen circumference. Because a delivered medication may be harmful to normal tissue, restriction of delivery to an actual abnormal target can be advantageous. For example, delivery of cyto-toxic material on one face of a lumen can be medically desirable while delivery of the same material to normal tissue on an opposite side of the lumen can be detrimental. 
         [0181]    In other exemplary embodiments the non radially symmetric distribution of holes  290  be used to inject two or more times at different circumferential portions of a lumen. Desired circumferential portions of the lumen can be selected by rotating valve  300  between ejection events. In an exemplary embodiment of the invention, multiple ejection events according to this strategy contribute to a more homogeneous delivery of medication throughout the target. 
         [0182]    In other exemplary embodiments of the invention, balloon  280  is non-cylindrical. Non cylindrical balloons  280  can optionally be symmetric or non symmetric. Holes  290  and/or  292  can be provided on any desired portion of balloon  280  to provided ejection of medication in a desired direction. Design and potential clinical applications of exemplary non-cylindrical balloons are described in co-pending U.S. patent application 2006/0190022 which is fully incorporated herein by reference. Additional exemplary balloon configurations are described below in. 
         [0183]    In an exemplary embodiment of the invention, markers are provided on balloon  280  to aid in orientation of balloon  280  within the body so that ejection of medication in a desired direction can be achieved. Optionally, the markers are radio-opaque markers  850  ( FIG. 8 ) so that they can be detected in X-ray or fluoroscopy images. 
         [0184]    According to exemplary embodiments of the invention, acceleration of fluid can occur in lumen  282  and/or in holes  290  and/or after exiting holes  290 . 
         [0185]    Optionally, holes  290  are configured as truncated cones. For example each hole  290  can have a diameter of 20μ at an inner surface of balloon  280  and a diameter of 25μ at the outer surface of balloon  280 . Due to mass conservation (V*A=V*A) the velocity of the fluid decreases while flowing in the channel. Optionally, the velocity of the fluid decreases in the hole and the fluid accelerates according to Bernoulli&#39;s principle when leaving the channel where the pressure is reduced to substantially zero. 
         [0186]    Exemplary Ejection Control Mechanism 
         [0187]    As described above, pressure in lumen  282  tends to decrease in distal portions of a cylindrical balloon  280  due to release of pressure from holes  290  in a proximal portion of the balloon. This can contribute to reduced ejection velocity and/or volume from holes located in a distal portion of balloon  280 . However, it is possible to inject medication several times from the same balloon  280 . 
         [0188]    In an exemplary embodiment of the invention, an axially translatable sleeve is provided between balloon  280  and vessel  310 . Optionally, the sleeve is positioned so that it does not cover any of holes  290  and/or  292  in an initial operational cycle of valve  300 . With each subsequent operational cycle, the sleeve is moved axially distally so that an increasing portion of proximal holes  290  and/or  292  are covered. In an exemplary embodiment of the invention, pressure T in inner balloon  270  insures contact between outer balloon  280  and the sleeve. Optionally, a pressure in inner balloon  270  can be reduced to make it easier to advance the sleeve along outer balloon  280  within vessel  310 . 
         [0189]    Use of the sleeve to cover a subset of holes  290  and/or  292  can reduce dissipation of pressure in lumen  282  in a proximal portion of balloon  280 , wherein the proximal portion increases with each successive operational cycle. 
         [0190]    In other exemplary embodiments of the invention only one ring of holes  290  is provided on balloon  280 . According to these embodiments of the invention, valve  300  is opened once as described above to provide an initial injection into a portion of a target. Valve  300  can then be repositioned one or more times and re-opened to inject into additional portions of the target. In an exemplary embodiment of the invention, the one ring of holes  290  is positioned on a distal portion of balloon  280 . Optionally, a series of injections into a site of former stenosis  320  are performed as valve  300  is being withdrawn after PTCA. 
         [0191]    In other exemplary embodiments of the invention a sleeve with one or more openings is provided. The openings can be configured to include a desired subset of holes  290 . Optionally, axially and/or rotational translation of the sleeve with respect to outer balloon  280  between injections can be used to sequentially eject medication from different subsets of holes  290 . Pulse wave delivery. 
         [0192]    Delivery of a pressure pulse to provide P inj  in lumen  282  of balloon  280  can be achieved using a wide variety of pressure sources. 
         [0193]    Exemplary pulse guns suited for use in the context of exemplary embodiments of the invention can be found in the field of needless injectors where the injection is performed through one orifice of about 100 μm diameter. For example, U.S. Pat. No. 5,730,723 (the disclosure of which is fully incorporated herein by reference) is an example of a gas powered gun and U.S. Pat. No. 5,704,911 (the disclosure of which is fully incorporated herein by reference) is an example of a spring loaded gun. In an exemplary embodiment of the invention, the single 100 μm hole of the needless injectors described in these earlier patents is replace by holes  290  of balloon  280 . Optionally, a total cross sectional area of holes  290  is 0.04, 0.5, 1, 2, 3, 4 or 5 mm or lesser or greater or intermediate areas. 
         [0194]      FIGS. 4A and 4B  are lateral cross sectional views of a spring activated pulse gun  214  according to an exemplary embodiment of the invention in “cocked” and “fired” states respectively. The depicted exemplary pulse gun comprises a housing  418 , a screw handle  410  to load the gun, a spring  412 , a piston  416 , a floating piston  420 , a medication reservoir  422 , a fill connector  424  and, an optional trigger  430  an exit port  426 . 
         [0195]    As seen in  FIG. 2A , exit port  426  is optionally connected to tubing  216  which is, in turn, connected to lumen  256  of catheter  250 . In this way, fluid exiting port  426  can be routed to lumen  282  of outer balloon  280 . In different exemplary embodiments of the invention, an optional fill connector  424  is attached to a medication vial (not shown) or to tubing  216  attached to an output from pump  212 . Optional fill connector  424  permits an inflow of medication to reservoir  422  when gun  214  is cocked. Optionally, a single gun  214  can deliver more than one medication during a treatment, for example by stepping release of piston  416  by trigger  430 . 
         [0196]      FIG. 4A  illustrates cocking of gun  214  to store energy as compression in spring  412  and fill medication reservoir  422  with medication. Withdrawal of handle  410  against resistive force of spring  412  increases a volume of medication reservoir  422  by causing floating piston  420  to move towards handle  410 . In an exemplary embodiment of the invention, motion of piston  420  draws medication into reservoir  422  from fill connector  424 . Connector  424  is optionally equipped with a directional pressure sensitive valve and/or stopcock so that medication is directed to exit port  426  when gun  214  is fired. Optionally, trigger  430  locks handle  410  in an extended position by engaging piston  416  so that gun  214  can easily be maintained in a “cocked” operative state. 
         [0197]      FIG. 4B  illustrates firing of gun  214 . Operation of optional trigger  430 , or release of handle  410  by other means, allows force stored in spring  412  to propel piston  416  forward. Forward motion of piston  416  drives floating piston  420  forwards and reduce a volume of medication reservoir  422 . This reduction in volume creates a sudden increase in pressure in medication reservoir  422 . In an exemplary embodiment of the invention, floating piston  420  traverses medication reservoir  422  and effectively reduces a volume thereof to zero. A resultant pressure pulse propels medication from reservoir  422  outwards through exit port  426  and through lumen  256  of catheter  250  as described above. Optionally, floating piston  420  is equipped with on O-ring or similar seal to reduce unwanted leaking of medication from medication reservoir  422   
         [0198]    Optionally, lumen  256  has a cross-sectional area of 0.22-0.4 mm 2  and a length of 1000 mm so that a total volume of lumen  256  is about 0.22-0.4 cc. Optionally, an aliquot of medication in reservoir  422  has a volume of 0.05 to 0.2 cc, optionally about 0.1 cc. In an exemplary embodiment of the invention, delivery of a single pulse from gun  214  causes a 50 to 90 percent increase in pressure in lumen  256 . This pressure causes holes  290  to open which dissipates the added pressure as described above by permitting medication to exit holes  290 . Optionally, flow of the medication in lumen  256  continues even when pressure is dissipated by ejection of fluid from holes  290  due to continued movement of floating piston  420 . 
       Exemplary Pulse Wave Amplification 
       [0199]    In an exemplary embodiment of the invention, delivery of a pressure pulse to provide P inj  in lumen  282  of balloon  280  is timed to coincide with a withdrawal of a small volume of fluid from lumen  272  of inner balloon  270 . Withdrawal of a small volume of fluid from lumen  272  of inner balloon  270  can be accomplished, for example, by reversing a flow direction of pump  210  for a short period of time. In an exemplary embodiment of the invention, withdrawal of a small volume of fluid from lumen  272  of inner balloon  270  imparts compliance to balloon  270  and/or increases an available volume of inner lumen  282  of outer balloon  280  to a small degree. Optionally, one or more of these effects reduce P inj  slightly so that an effect of the pulse wave delivered by gun  214  is amplified. 
       Exemplary Conduit Construction 
       [0200]      FIG. 2A  shows a system of conduits which conduct fluids from pumps  210  and  212  and from gun  214  to valve  300 . In the depicted embodiment, tubing  216  from pumps  210  and  212  and from gun  214  converges at connector  220 . Between connector  220  and catheter  250 , a conduit  226  conducts fluid destined to inner lumen  282  of outer balloon  280  and fluid destined to inner lumen  272  of inner balloon  270 . 
         [0201]      FIG. 2C  depicts an exemplary embodiment of conduit  226  in a cross section at A-A. In the depicted embodiment, conduit lumen  256  is nested within conduit lumen  254 . Optionally, an outer wall of lumen  254  is constructed of Nylon or a stronger material such as, for example, PEEK and an outer wall of lumen  256  is constructed of SS  304 . In an exemplary embodiment of the invention, conduit  226  is 600, optionally 800, optionally 1000 mm long or lesser or intermediate or greater lengths. In an exemplary embodiment of the invention, a shorter conduit  226  contributes to a reduction in dissipation of a pressure pulse emanating from gun  214 . 
         [0202]      FIG. 2B  is a cross section of catheter  250  at B-B illustrating catheter lumens  254  and  256  which are extensions of similarly numbered conduit lumens. Optionally, catheter  250  includes a third lumen  252  for guidewire  260 . In  FIG. 2B  the three lumens of catheter  250  are depicted in an exemplary parallel non-concentric configuration. In other exemplary embodiments of the invention, the lumens can be arranged concentrically. 
         [0203]      FIG. 2D  shows an alternate exemplary parallel non-concentric configuration of the three catheter lumens at B-B. In the pictured embodiment lumen  256  is increased in cross sectional area. Optionally, providing at least a portion of the outline of lumen  256  as a concave curve contributes to the increase in cross sectional area. 
       Exemplary Construction Considerations 
       [0204]    Optionally, pump  210  and/or pump  212  are standard PTCA pumps such as, for example those produced by Johnson and Johnson (e.g. deflator MX1380LB) or Medtronics (e.g. indeflator AC2200 Minneapolis, Minn.; USA). 
         [0205]    In an exemplary embodiment of the invention, tubing  216  is hypo tubing, for example of the type manufactured by Creganna Medical Devices (Galway; Ireland; UK) In an exemplary embodiment of the invention, outer balloon  280  is constructed of an elastic material such as for example, nylon. Optionally, the nylon is 15, 20, 25, 30, 35, or 40 μm thick. Nylon suitable for use in construction of balloons  280  may be purchased, for example, from Polymerex Medical Corp (San Diego, Calif., USA). 
         [0206]    Optionally, increasing thickness of the nylon used to construct outer balloon  280  increase strength of the balloon and/or reduces elasticity thereof. 
         [0207]    In various exemplary embodiments of the invention, inner balloon  270  can be constructed of an elastic material or an inelastic material. 
         [0208]    Suitable elastic materials for construction of balloon  270  include, but are not limited to nylon as described above for outer balloon  280 . 
         [0209]    Suitable inelastic (relative to Nylon) materials for construction of balloon  270  include, but are not limited to PET such as that manufactured by Advance Polymer (Salem, N.H., USA). 
         [0210]    Optionally, an elastic inner balloon  270  “snaps back” as pressure in lumen  282  decreases from P inj  (or greater) to T and then below T. In an exemplary embodiment of the invention, the “snapping back” can cause additional ejection of medication from holes  290 . In an exemplary embodiment of the invention, energy provided by “snapping back” can substitute for a portion of the energy pulse provided by gun  214 . In an exemplary embodiment of the invention, “snapping back” occurs rapidly enough to become part of the ejection of medication, which optionally persists 5 to 100 milliseconds. 
         [0211]    In an exemplary embodiment of the invention, holes  290  in balloon  280  are prepared by micro-drilling. Micro-drilling equipment is available, for example, from Spectralytics (South Dassel, Minn.; USA). 
         [0212]    Exemplary catheters  250  of the type described above may be manufactured, for example, by Minnesota MedTec (Minneapolis, Minn.; USA). 
       Exemplary Medical Protocols 
       [0213]    Optionally, valves according to the invention may be sized for specific applications. For example, in some exemplary embodiments of the invention, a valve for coronary applications might have a diameter of 2 to 3.5 mm and a length of 10 to 25 mm. 
         [0214]    According to other exemplary embodiments of the invention, a valve intended for deployment in the prostate might be considerably larger, for example a diameter of 6 to 11 mm and a length of 20 to 40 mm. 
         [0215]    Alternatively or additionally, particular modifications may be desired for certain vessel types. For example, the aorta is thicker, while a coronary vessel is thinner, thus suggesting different ejection parameters, powers and/or P inj  and sizes. For example, an aorta may be 3 mm thick, while a coronary vessel may be less than 1 mm thick. 
         [0216]    Exemplary Injection Results 
         [0217]      FIG. 6  is a micrograph  600  illustrating exemplary injection results from injection of a solution including black dye into an arterial wall using a valve  300  according to an exemplary embodiment of the invention. Micrograph  600  is a representative field of view of tissue injected with a valve  300  including an outer balloon  280  with 128 holes  290  characterized by a 20 μm diameter. A 120 atmosphere pulse pressure (PP) was provided by a gun  214  of the type depicted in  FIG. 4A  and described above. A volume of 0.1 cc was ejected from gun  214 . The inner balloon  270  was inflated with 12 atmospheres of pressure. Under these conditions P inj  is estimated to be in the range of 16-25 atmospheres following delivery of the pressure pulse from gun  214 . 
         [0218]    After injection the artery was removed, fixed in 4% paraformaldehyde and embedded in paraffin. A microtome was used to cut 4 μm sections which were mounted on glass slides and de-parafinized and stained with Haemotoxylin/Eosin using standard protocols. Black dye (seen most clearly at  620 ) from the injection penetrated intimae  640  and arrived deep within media  650  but did not reach adventitia  630  of the arterial wall. 
         [0219]    Measurements are provided to serve only as exemplary measurements for particular cases. The exact measurements stated in the text may vary depending on the application, the type of vessel (e.g., artery, vein, xenograft, synthetic graft), shape of plaque (e.g., local, elongate, thin, thick, outer remolding, vulnerable) and/or sizes of vessels involved (e.g., 1 mm, 2 mm, 3 mm, 5 mm, aorta sized). 
         [0220]    A wide variety of medications may be injected by apparatus or methods according to exemplary embodiments of the invention. Medications can include, but are not limited to, structural materials, anti-clotting agents, anti-cell proliferation agents, cytotoxic materials (e.g. chemotherapeutic agents, organic solvents (e.g. alcohols), fibrotic agents and metals (e.g. gold). Fibrotic agents may include, but are not limited to, formalin, papavain and curarc. 
         [0221]    In an exemplary embodiment of the invention, induction of fibrosis in the target tissue can block an electrical signal. Blocking of an electric signal can contribute to regulation of cardiac rhythm. 
         [0222]    In an exemplary embodiment of the invention, cytotoxicity is desirable, for example in tumor treatment or other targeted tissue ablation. Targeted tissue ablation may have applications, for example, in treatment of atrial fibrillation and/or to mimic the effects of intestinal resection. 
       Exemplary Pressure Profile 
       [0223]      FIG. 9  is a graph illustrating pressure in outer balloon  280  (solid line) and inner balloon  270  (dashed line) of an exemplary valve  300  of the general configuration described above as a function of time prior to, during, and after an exemplary injection event. 
         [0224]    In an exemplary embodiment of the invention, after valve  300  is positioned at a desired location pump  210  is operated and inner balloon  270  is inflated to T (e.g. 10 atmospheres). In the depicted embodiment, all holes  290  are closed at this stage. Pump  212  is then operated to bring a pressure in lumen  282  of balloon  280  to a pre-inflation pressure slightly below T (e.g. 8 atmospheres). 
         [0225]    In an exemplary embodiment of the invention, a subsequent pressure pulse causes pressure in lumen  282  to exceed P inj . At least some of holes  290  open at this stage. Optionally, pressure in lumen  272  of inner balloon  270  also rises slightly as pressure in lumen  282  of outer balloon  280  causes inner balloon  270  to contract. 
         [0226]    In the depicted embodiment, the delivered pulse continues to increase pressure in lumen  282 . Optionally, pressure in lumen  282  may exceed T by 4, 8, 12, 16 or 20 atmospheres or lesser or greater or intermediate pressure differentials. The pressure differential drives injection of liquid medication from holes  290  into surrounding tissue. 
         [0227]    After the pulse, pressure in lumen  282  begins to decrease and eventually drops below P inj  , at which point holes  290  close. In the depicted embodiment, pressure in lumen  282  of outer balloon  280  drops momentarily below the pre-inflation pressure. Optionally, pump  212  brings pressure in lumen  282  of outer balloon  280  back to the pre-inflation pressure and valve  300  is ready to receive an additional pulse. 
       Exemplary use in Conjunction with Atherectomy 
       [0228]    In an exemplary embodiment of the invention, valve  300  (or  302  or  304  or other exemplary configurations) is used to deliver medication to an atherectomy site during or shortly after performance of the atherectomy. 
         [0229]    Atherectomy may be performed, for example, using commercially available devices. 
         [0230]    One commercially available atherectomy device is a Rotoblator (Heart Technology Inc., Bellevue, Wash., USA). Rotoblator type devices and Atherectomy procedures using same are described in, for example, U.S. Pat. Nos. 4,990,134; 5,314,407 and 5,364,393, the disclosures 
         [0231]    Another commercially available atherectomy device is a “SilverHawk™” (Fox Hollow Technologies Inc., Menlo Park, Calif., USA). SilverHawk type devices and Atherectomy procedures using same are described in, for example, U.S. Pat. Nos. 6,027,514; 6,447,525; 6,629,953 and 6,638,233 the disclosures of which are fully incorporated herein by reference. 
         [0232]    As in PTCA, atherectomy sites are prone to restenosis and/or arterial collapse. Delivery of appropriate medications as described above for PTCA is potentially beneficial in the context of an atherectomy procedure. 
         [0233]    Atherectomy catheters that include imaging capabilities are described at least in U.S. Pat. Nos. 6,299,622; 6,623,496 and 6,997,934 the disclosures of which are incorporated herein by reference. 
         [0234]    In an exemplary embodiment of the invention, a pressure sensitive valve according to one of the exemplary embodiments described above (e.g. valve  300 ) is installed on an atherectomy catheter behind the working head. As the working head traverses the stenosis, the valve is brought into proximity with the stenosis. Medication can be injected into vessel wall  310  and/or stenosis  320  as described above. Optionally, a catheter with imaging capabilities is used to align holes  290  with a desired target. 
         [0235]    Exemplary Force Diagrams 
         [0236]      FIGS. 10A and 10B  are diagrams illustrating an exemplary interplay of forces in an exemplary valve according to the invention. X is used here to indicate a constant. 
         [0237]      FIG. 10A  illustrates a theoretical interplay of forces between two masses M 1  and M 2 , each supported by a separate spring and M 2  partially resting on M 1 . As illustrated, an expansive pressure P provided by the spring of M 1  can be expressed as Kn*Xn. The mass of M 1  provides an opposing force with a magnitude K 1 *X 1 . In the depicted configuration M 1  and M 2  are in a steady state so that a downward force exerted by M 2  on its spring (K 2 *X 2 ) is equal to P−[K 1 *X 1 ]. 
         [0238]      FIG. 10B  shows an analogous situation with outer balloon  280  replacing M 2  and inner balloon  270  replacing M 1  the “springs” in this diagram represent the contractive force supplied by the coefficient of elasticity K of each balloon. Inner balloon  270  is inflated with a pressure P which is partially overcome by K 1  of the inner balloon. When inner balloon  270  is inflated so that it conforms to outer balloon  280 , K 2  of the outer balloon is equal to P−[K 1 ]. According to the depicted embodiment, P inj  will be any pressure sufficient to overcome K 2  and cause balloon  280  to move away from balloon  270  so that lumen  282  expands to permit a flow of fluid outwards from hole(s)  290 . 
         [0239]    A variety of numerical indicators have been utilized to describe dimensions of various components of the apparatus and/or operational pressures. These numerical indicators are exemplary only and could vary even further based upon a variety of engineering principles, materials, intended use and designs incorporated into the invention. 
         [0240]    In addition individual features described herein can be used together, separately or in various sub-combinations. Alternatively or additionally, features described in the context of an apparatus may be applied to a method, and features described in the context of a method may be applied to an apparatus. 
         [0241]    In an exemplary embodiment of the invention, an apparatus according to the invention is supplied as a kit including instructions for use and/or a medication. Optionally, the medication is provided as a pre-measured dose. Optionally, the pre-measure dose is pre-loaded into a catheter lumen and/or pulse gun. In an exemplary embodiment of the invention, use of an apparatus as described above reduces waste of medication. The examples presented are not intended to limit the scope of the invention, which is defined by the following claims. 
         [0242]    The terms “include”, “comprise” and “have” and their conjugates as used herein mean “including but not necessarily limited to”.