Abstract:
A method including introducing a treatment device via a transluminal route within a blood vessel to a treatment site including a vulnerable plaque; and dispensing a treatment agent including a compound having a property that tends to modify a property of a content of the vulnerable plaque. A kit including a first treatment agent including a property capable of modifying a property of a content of a vulnerable plaque; and a different second treatment agent. A composition including a treatment agent capable of modifying the mobility of a content of a vulnerable plaque in a form and concentration suitable for dispensing through a catheter into a blood vessel.

Description:
FIELD  
       [0001]     Transluminal treatment devices, compositions, and methods.  
       BACKGROUND  
       [0002]     Thin-capped fibroatheroma (“TFCA”) or vulnerable plaque refers to an atherosclerotic plaque that may develop inside a blood vessel, such as an artery. The typical vulnerable plaque contains a core filled with lipids, cholesterol crystals and cholesterol esters, macrophages, and other cells. The core has a thin fibrous cap (0.05 millimeters (mm) to 0.10 mm thickness). The fibrous cap may become weakened and rupture. When ruptured, the luminal blood becomes exposed to highly thrombogenic material from the core of the vulnerable plaque, which can result in total thrombotic occlusion of the blood vessel.  
         [0003]     There is increasing evidence that the propensity of a vulnerable plaque to rupture is related to an activity of matrix metalloproteinases (“MMPs”), largely synthesized by macrophage-derived foam cells. Specifically, MMPs may degrade extracellular matrix proteins, such as Types I and III collagen that are a significant source of fibrous cap structural integrity. Thus, chronic and/or local inflammation, typically a result of monoctye adhesion, in the plaque can lead to destabilization of the vulnerable plaque and acute coronary syndromes (via thrombosis).  
         [0004]     Researchers believe that vulnerable plaque is formed in the following way. Fat droplets are absorbed by the blood vessel (e.g., artery), which causes the release of cytokines (proteins) that lead to inflammation. The cytokines make the artery wall sticky, which attracts monocytes (immune system cells). The monocytes squeeze into the artery wall. Once inside, the monocytes turn into macrophages (cells) and begin to soak-up fat droplets. The fat-filled macrophages form a plaque with a thin covering.  
         [0005]     Improvements in imaging techniques, such as optical coherence tomography (“OCT”) and intravascular ultrasound (“IVUS”) offer the opportunity to identify a vulnerable plaque. A need exists, however, for effective methods to treat (e.g., remove, immobilize, reshape) a vulnerable plaque.  
       SUMMARY  
       [0006]     A method is disclosed. In one embodiment, the method includes introducing a treatment device via a transluminal route within a blood vessel to a treatment site comprising a vulnerable plaque; and dispensing a treatment agent comprising a compound comprising a property that tends to modify a property of a content of the vulnerable plaque. Representative properties of the content of the vulnerable plaque include mobility. Suitable compounds include compounds that may act as a cross-linkers that can migrate (e.g., diffuse) into the core of the fibrous cap and cross-link the core materials (e.g., lipids) modifying the core materials from highly thrombogenic to generally non-thrombogenic.  
         [0007]     In another aspect, a kit is disclosed. In one embodiment, a kit includes a first treatment agent comprising a property capable of modifying the property of a content of a vulnerable plaque; and a second treatment agent such as an agent that accelerates a cross-linking of a content of a vulnerable plaque and the first treatment agent. In another embodiment, a kit includes a catheter suitable for traversing a blood vessel and having a length dimension suitable for placement at a treatment site within the blood vessel from an externally accessible point of a patient. The first treatment agent and/or the second treatment agent may be introduced through the catheter at a treatment site, including a vulnerable plaque to modify the vulnerable plaque.  
         [0008]     In another aspect, a composition is disclosed. The composition includes a treatment agent capable of modifying the mobility of a content of a vulnerable plaque in a form and concentration suitable for dispensing through a catheter into a blood vessel. Examples of a treatment agent capable of modifying the mobility of a content of a vulnerable plaque include cross-linking agents.  
         [0009]     In a further aspect, a system is described. In one embodiment, a system includes a system including a reservoir containing a first flowable substance including a cross-linking agent having a property that modifies a core of a vulnerable plaque, and a cannula including a lumen in fluid communication with the first flowable substance in the first reservoir and a distal end portion defining an opening allowing passage out of the distal end portion of the cannula. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]      FIG. 1  shows a cross-sectional schematic front view of a blood vessel including a vulnerable plaque.  
         [0011]      FIG. 2  shows a cross-sectional schematic front view of a vulnerable plaque where a core of the vulnerable plaque has been modified by a treatment agent.  
         [0012]      FIG. 3  shows a representative molecular level cross-linking of lipids of a vulnerable plaque core.  
         [0013]      FIG. 4  shows a schematic side view of a tri-lumen shaft catheter assembly.  
         [0014]      FIG. 5  shows a cross-sectional schematic side view of one embodiment of a distal portion of the catheter assembly of  FIG. 4 .  
         [0015]      FIG. 6  shows a cross-sectional view of the distal portion of the catheter assembly of  FIG. 4  through line A-A′ of  FIG. 5 .  
         [0016]      FIG. 7  shows a cross-sectional schematic side view of another embodiment of a distal portion of the catheter assembly of  FIG. 4 .  
         [0017]      FIG. 8  shows a cross-sectional view of the distal portion of the catheter assembly of  FIG. 4  through line A-A′ of  FIG. 7 .  
         [0018]      FIG. 9  shows a cross-sectional schematic side view of another embodiment of a distal portion of the catheter assembly of  FIG. 4 .  
         [0019]      FIG. 10  shows a cross-sectional schematic side view of a blood vessel having an embodiment of a catheter assembly described with reference to  FIGS. 4-6  disposed therein and dispensing a treatment agent at a point proximal to a vulnerable plaque.  
         [0020]      FIG. 11  shows a cross-sectional schematic side view of a blood vessel having an embodiment of a catheter assembly described with reference to  FIG. 4  and  FIGS. 7-8  disposed therein and dispensing a treatment agent with an occlusion feature at the vulnerable plaque.  
         [0021]      FIG. 12  shows a cross-sectional schematic side view of a blood vessel having an embodiment of a catheter assembly described with reference to  FIG. 4  and  FIG. 9  disposed therein and dispensing a treatment agent with an occlusion feature at the vulnerable plaque. 
     
    
     DETAILED DESCRIPTION  
       [0022]      FIG. 1  shows a cross-sectional view of a blood vessel, such as a coronary artery. Blood vessel  100  includes vessel wall  110  defining lumen  105  therethrough. Formed within lumen  105  of blood vessel  100  is vulnerable plaque  120 . Vulnerable plaque  120  includes core  130  surrounded by fibrous cap  140 . Core  130 , in an unmodified state, includes lipids, cholesterol crystals, cholesterol esters, macrophages, and other cells. Core material  130  in an untreated state is highly thrombogenic and only fibrous cap  140  prevents release of the thrombogenic materials.  
         [0023]      FIG. 2  shows blood vessel  100  following the modification of the core material of vulnerable plaque  120 . In one embodiment, a composition is introduced into vulnerable plaque  120  to immobilize the core material. Representatively, the core material may be immobilized by the introduction into vulnerable plaque  120  of a cross-linking agent. Cross-linking agents, in one sense, are agents that link two or more molecules or cells. In one embodiment, the cross-linking agents described herein are introduced in a form such that they cross-link core material of a vulnerable plaque. In one sense, the cross-linking agents may form a network of linked lipid cells within vulnerable plaque  120 . In this manner, the core material of vulnerable plaque  120  may be rendered substantially, predominantly, or totally immobile and thus less thrombogenic.  FIG. 2  shows vulnerable plaque  120  having modified (immobilized) core material  230 .  
         [0024]     In one embodiment, a suitable agent for cross-linking the core material of a vulnerable plaque is a glutaraldehyde. Another suitable compound is a polyepoxy. An example of a suitable polyepoxy is ethylene glycol diglycidyl ether. Ethylene glycol diglycidyl either is commercially available as DENACAL EX-810™ for Nagase Chemtex Corporation of Tatsuno City Hyogo Japan. In another embodiment, a suitable cross-linking agent is a natural compound, genipin. In another embodiment, the cross-linking agent is CNBr-activated sepharose. Each of the noted agents or compounds may be used alone or in combination.  
         [0025]     In one embodiment, the cross-linking agents are introduced into a blood vessel in liquid form and given the opportunity or caused to diffuse or migrate into a vulnerable plaque. In this manner, the fibrous cap of the vulnerable plaque is not disturbed. Thus, in one embodiment, the cross-linking agent(s) are of a molecular size such that the cross-linking agent(s) is/are capable of diffusing or migrating through a fibrous cap of a vulnerable plaque.  
         [0026]      FIG. 3  shows a representation of a cross-linking event.  FIG. 3  shows lipid cell  310  and lipid cell  320  that might be present in core material of a vulnerable plaque. In this embodiment, lipid cell  310  and lipid cell  320  are connected, such as by a covalent bond connection to cross-linker  330 . Cross-linker  330 , in one embodiment, is selected from a glutaraldehyde, a polyepoxy, genipin and CNBr-activated sepharose. While not wishing to be bound by theory, it is believed lipid cells of the core material have surface amine groups available for chemical bonding. Thus, one of the noted cross-linking agents may cross-link to lipid cells through covalent bonds  325  formed between the amine groups on different lipid cells. Since the cross-linking event occurs within a vulnerable plaque, the lumen of the blood vessel including the vulnerable plaque is not occluded by the cross-linking event.  
         [0027]     Each of the above-referenced cross-linking agents is capable of achieving or inducing a cross-linking event. Each of the treatment agents may be delivered without a cross-linkable monomer or polymer and thus all or a substantial amount of the cross-linking agent is available to cross-link a material of the core of a vulnerable plaque.  
         [0028]     To increase the immobilization or fixation time of a core material of a vulnerable plaque, an accelerator may be introduced. An example of a suitable accelerator is salicylic acid. Salicylic acid can increase the reaction time of the noted cross-linking agents (e.g., the time to immobilize the vulnerable plaque tissue), particularly when administered in an alkaline pH. A preferable pH range is on the order of 10 to 12. A representative amount of salicylic acid as an accelerator is on the order of 0.1 percent to one percent accelerator to fixation agent.  
         [0029]     The accelerator may be separately introduced into the vulnerable plaque, such as before or after the introduction of a cross-linking agent or simultaneously with the cross-linking agent (such as in a mixture). In one embodiment, a mixture of a cross-linking agent and an accelerator is prepared on site moments before introduction into a blood vessel to minimize the possible cross-linking of the mixture prior to introduction.  
         [0030]     In addition to an accelerator, additional therapeutic compounds may alternatively or additionally be introduced into a vulnerable plaque. Representative therapeutic compounds include those that inhibit a vulnerable plaque from growing. Example include enzyme inhibitors and cytotoxic agents.  
         [0031]     In one embodiment, the combination of a treatment agent, an accelerator, and any other therapeutic compound for introduction into a vulnerable plaque may be provided as a kit. Representatively, a kit may include separate amounts of each of a treatment agent (a cross-linking agent), an accelerator, and any other optional therapeutic agents. The agent(s) and accelerator may be in a form and dosage suitable for direct infusion into a blood vessel. Instructions may also be provided on infusion of treatment agent(s) or combining treatment agents and/or accelerators. In another embodiment, a kit may include a catheter assembly for delivering the treatment agent to a blood vessel.  
         [0032]      FIG. 4  shows a side view of an embodiment of a catheter assembly suitable for introducing a treatment agent into a blood vessel. In this embodiment, catheter assembly  400  includes distal portion  410  for insertion into a body lumen, such as a blood vessel, and portion  420  intended to remain external to a patient when catheter assembly  400  is in use. Catheter assembly  400  includes primary cannula or tubular member  425  extending from proximal portion  420  through distal portion  410 . In one embodiment, primary cannula  425  has a length such that catheter assembly  400  may be percutaneously inserted into either a femoral artery or a radial artery and advanced to a coronary artery (e.g., left coronary artery, left anterior descending artery, right coronary artery, etc.).  
         [0033]     In one embodiment, catheter assembly  400  accommodates three cannulas (a three-lumen shaft).  FIG. 5  illustrates a magnified view of distal portion  410  of catheter assembly  400 .  FIG. 6  shows a cross-section of catheter assembly, through line A-A′ of  FIG. 5 . Referring to  FIG. 5  and  FIG. 6 , three cannulas or tubular members are shown within a lumen of primary cannula  425 . The cannulas include guidewire cannula  530 , inflation cannula  540 , and infusion cannula  550 . Each cannula has a lumen therethrough.  
         [0034]      FIG. 5  also shows balloon  520  connected to primary cannula  425 . Balloon  520  is illustrated in an inflated state. Balloon  520  may be inflated through inflation cannula  540 . Inflation cannula  540  extends through primary cannula  425  from proximal portion  420  and distally terminates within balloon  520 . In one embodiment, balloon  520  is selectively inflatable through inflation cannula  540  to dilate from a collapsed configuration to a desired and controlled expanded configuration. Balloon  520  can be selectively inflated by supplying a fluid (e.g., liquid) into a lumen of inflation cannula  540  at a predetermined rate of pressure. Likewise, balloon  520  is selectively deflatable to return to a collapsed configuration or a deflated profile.  
         [0035]     Balloon  520  can be made from various materials, including, but not limited to, polymers and copolymers of polyolefins, polyamides, polyester and the like. The specific material employed should be compatible with the inflation or expansion fluid and must be able to tolerate the pressures that are developed within balloons  520 . One suitable material is an elastomeric nylon, such as PEBAX 63D™, a condensation polymerized polyether block polyamide.  
         [0036]     A wall of balloon  520  can have any suitable thickness so long as the thickness does not compromise properties that are critical for achieving optimum performance. Relevant properties include, but are not limited to, high burst strength, low compliance, good flexibility, high resistance to fatigue, the ability to fold, the ability to cross and re-cross a desired region of interest and low susceptibility to defects caused by handling. By way of example, not limitation, a suitable thickness of a balloon wall can be in the range of 0.0005 inches to 0.002 inches, the specific specifications depending on, among other considerations, the anatomy and size of the target lumen in which balloon  520  is to be inserted.  
         [0037]     As noted above, catheter assembly  400  also includes guidewire cannula  530  disposed through at least a portion of primary cannula  425 . Guidewire cannula  530  allows catheter assembly  400  to be fed and maneuvered over a guidewire (not shown). In one embodiment, guidewire cannula  530  extends the length of primary cannula  425  from proximal portion  420  of catheter assembly  400  to distal portion  410 . Representatively, in a typical procedure, the guidewire may be initially placed through a region of interest in a physiological lumen (e.g., a blood vessel) and catheter assembly  400  is advanced, possibly through a guide catheter, on/over the guidewire to or through a region of interest in an over the wire (OTW) fashion. In another embodiment, catheter assembly  400  is a rapid exchange (RX) type catheter assembly and only a portion of catheter assembly  400  (a distal portion) is advanced over the guidewire. In rapid exchange catheters, typically the guidewire cannula/lumen extends from the distal end of the catheter to a proximal guidewire port spaced distally from the proximal end of the catheter. The proximal guidewire port is typically spaced a substantial distance from the proximal end of the catheter.  
         [0038]     As also mentioned above, primary cannula  425  includes infusion cannula  550 . Infusion cannula  550  extends from proximal portion  420  through distal portion  410  of catheter assembly  400 . In this embodiment, infusion cannula  550  extends beyond a distal portion of balloon  520 , defining an infusion or dispensing port.  
         [0039]     Infusion port  555  has a position distal to balloon  520 . In the illustrated embodiment, infusion port  555  is in the distal-most end of the catheter. In other embodiments (not shown), infusion port  555  could be one or more lateral ports in the sidewall of the catheter shaft. In this manner, balloon  520  is placed in a blood vessel longitudinally adjacent and either downstream or upstream to the vulnerable plaque to occlude blood flow along the vulnerable plaque. Balloon  520  may be used to occlude the blood vessel and minimize blood flow during a procedure to treat (e.g., modify, immobilize, etc.) the vulnerable plaque. In the embodiment shown in  FIGS. 4-6 , balloon  520  could be placed upstream of a vulnerable plaque to occlude flow along the vulnerable plaque. A treatment agent could then introduced into the blood vessel through infusion port  555 .  
         [0040]     In the embodiment shown in  FIGS. 4-6 , each of guidewire cannula  530  and inflation cannula  540  extend beyond balloon  520 . It is appreciated that a guidewire may or may not be in place during infusion of a treatment agent through a lumen of inflation cannula  540 . In another embodiment, rather than having a separate infusion cannula, a guidewire cannula may be used for a guidewire and providing a lumen for a treatment agent. Representatively, in the assembly shown in  FIGS. 4-6 , catheter assembly  400  would be placed at a region of interest using a guidewire. After placement, the guidewire would be removed and a treatment agent source (reservoir) connected to a proximal end of guidewire cannula  530  to deliver the treatment agent through a lumen of guidewire cannula  530 .  
         [0041]     Referring again to the embodiment shown in  FIG. 4 , proximal portion  420  of catheter assembly  400  includes indeflator  440  for introducing a liquid into inflation cannula  540 . In one embodiment, indeflator  440  introduces an inflation fluid into a lumen of cannula  540  to inflate balloon  520  at a predetermined rate of pressure.  FIG. 4  also shows indeflator  450  capable of introducing a treatment agent into a lumen of infusion cannula  550 . In one embodiment, indeflator  450  is a controlled volume indeflator such that a predetermined volume of the treatment agent may be introduced into a lumen of infusion cannula  550  and therefore at a treatment site.  FIG. 4  illustrates several reservoirs that may be connected to indeflator  450 . Reservoir  460  contains, for example, a treatment agent such as a glutaraldelhyde, a polyepoxy, a natural compound such as genipin, or an activated sepharose. Optional reservoir  470  contains an accelerator such as salicylic acid. Optional reservoir  480  contains a therapeutic agent other than a cross-linking agent. In one embodiment, where multiple agents are to be delivered from multiple reservoirs, the reservoirs may be sequentially connected to indeflator  450 .  
         [0042]     In the embodiment shown in  FIG. 4 , indeflator  440  is shown in an offset or lateral position relative to primary cannula  425 . In another embodiment, indeflator  440  and a proximal portion of inflation cannula  540  may be arranged coaxially with primary cannula  425  similar to infusion cannula  550  and indeflator  450 .  
         [0043]     In the embodiment described with reference to  FIG. 4 ,  FIG. 5  and  FIG. 6 , catheter assembly  400  includes a balloon having as at least one purpose to occlude a blood vessel at a position proximal to a treatment site (e.g., a position proximal to a vulnerable plaque). In this manner, infusion cannula  550  and port  555  is extended distally beyond a distal end of the balloon. In another embodiment, it may be desirable to place an occluding feature, such as an occluding balloon at (e.g., radially adjacent) a treatment site (e.g., at a vulnerable plaque). In this embodiment, the treatment agent would be introduced through the occluding feature.  
         [0044]      FIG. 7  and  FIG. 8  show an alternative embodiment of distal portion  410  of catheter assembly  400 , including a balloon having a porous portion and an infusion port within the balloon.  FIG. 7  shows balloon  720  connected to primary cannula  425 . Guidewire cannula  730  extends beyond a distal end of balloon  720 . Infusion cannula  750  terminates within balloon  720  at infusion port  755 . In this embodiment, treatment agent will be introduced at a proximal end of infusion cannula  750 , through a lumen of infusion cannula  750  to inflate balloon as well as to migrate to a vulnerable plaque through a porous portion of balloon  720 . Since a treatment agent will be used to inflate balloon  720 , a separate inflation cannula/lumen is not necessary. In alternate embodiment, catheter assembly may include an infusion cannula and an inflation cannula.  
         [0045]     In one embodiment, balloon  720  includes porous portion  725 . In this embodiment, balloon  720  also includes proximal skirt  770  connected to primary cannula  425 , medial working length  775 , and distal skirt  780  connected to distally extending guidewire cannula  730 . In one embodiment, porous portion  725  may make up a portion of less than the entire inflatable portion of balloon  720 . Porous portion  725  in one embodiment, for example, extends only partially around the circumference of balloon  720 .  FIG. 8  shows a cross-section through line A-A′ of  FIG. 7  and illustrates porous portion  725  extending partially around the circumference of balloon  720 . In one embodiment, porous portion  725  extends a working length of balloon  720  (e.g., the length of medial working length  775 ), ranging in length from eight millimeters (mm) to 28 mm depending on the length of a vulnerable plaque. In another embodiment, porous portion  725  extends only partially around the circumference of balloon  720  and extends a length less than the length of medial working length  775  of balloon  720 .  
         [0046]     A porous balloon or a balloon having a porous portion may be made from expanded polytetrafluoroethylene (ePTFE). A balloon having a porous portion of ePTFE may be made with pore sizes on the order of five microns (μm) to 40 μm. One way to form a partial porosity ePTFE balloon is by masking a desired porous portion with a pressure sensitive tape such as Scotch tape and impregnating the remaining portion of balloon with a solution of an elastomeric polymer such as styrene-butadiene-styrene elastomer, silicone-polyurethane co-polymer, or polyurethane, etc. Another way to form a non-ePTFE balloon that has a porous portion is to create multiple holes range from 25 to 250 micrometers on a balloon surface via mechanical or chemical means.  
         [0047]     In the above described embodiment, infusion cannula  750  delivers treatment agent to an interior of balloon  720  to inflate balloon  720 . The treatment agent migrates from balloon  720  through pores in porous portion  725  of balloon  720 . It is appreciated that other configurations are also possible. For example, a catheter assembly may include a separate inflation cannula and an infusion cannula, with the inflation cannula extending into a first balloon and the infusion cannula extending into a second balloon disposed on/over the first balloon. In this manner, the first balloon may be used to occlude at least a portion of a vessel and the second balloon may serve to partially occlude the vessel and to deliver the treatment agent. In another embodiment, two balloons may be used and fed by a single infusion cannula. An infusion cannula may extend into a first balloon that is porous (e.g., contains micropores) and allows a treatment agent to migrate from an interior of the first balloon into an interior of the second balloon on/over the first balloon. The second balloon has a portion that is also porous allowing the treatment agent to migrate from the interior of the second balloon. One advantage of this configuration is that the second balloon provides a protective effect to a vessel from possible pressurized streams of treatment agent that may come from the first inner balloon.  
         [0048]     In the embodiment described with reference to  FIG. 7  and  FIG. 8 , a balloon is placed so that a portion of its working length is at or along a fibrous cap of a vulnerable plaque. Care may be necessary to not contact the fibrous cap or minimize the force of contact on the fibrous cap when the balloon is inflated.  FIG. 9  shows an alternative embodiment of distal portion  410  of catheter assembly  400 , including a balloon having a porous portion and an infusion port within the balloon.  FIG. 9  shows balloon  920  connected to primary cannula  425 . Guidewire cannula  930  extends beyond a distal end of balloon  920 . A distal end of infusion cannula  950  terminates within balloon  920  at infusion port  955 . Treatment agent may be introduced at a proximal end of infusion cannula  950  through infusion cannula  950 , and through infusion port  955  to inflate balloon  920 .  
         [0049]     In the embodiment illustrated in  FIG. 9 , balloon  920  includes proximal skirt  970  connected to primary cannula  425  and distal skirt  980  connected to guidewire cannula  930 . Balloon  920  also includes first medial working length portion  974  and second medial working length portion  975  connected to proximal skirt  970  and distal skirt  980 , respectively. In an inflated state, first medial working length portion  974  has a greater diameter than second medial working length protion  975  and is generally more elastic than second medial working length portion  975 . One way to form first medial working length portion  974  having a greater elasticity than second medial working length portion  975  to form a generally inelastic medial working length of balloon  920  having a length including both first medial working length portion  974  and second medial working length portion  975  and then impregnate an elastomer into first medial working length portion  974 .  
         [0050]     In one embodiment, first medial working length portion  974  is capable of being inflated to a diameter of a target blood vessel while second medial working length portion  975  may be inflated to a diameter less than a diameter of a target blood vessel and preferably less than a diameter of a blood vessel including a vulnerable plaque. In one embodiment, catheter assembly  400  is placed so that first medial working length portion  974  of balloon  920  is upstream of a vulnerable plaque and can be inflated to occlude a target blood vessel without contacting a vulnerable plaque.  
         [0051]     First medial working length portion  974  has a length dimension suitable to provide the structural integrity to occlude blood flow. Representatively, a length on the order of a few millimeters is sufficient.  
         [0052]     Second medial working length portion  975  of balloon  920  has a length, in one embodiment, approximately equivalent to a length of a vulnerable plaque. A representative length for second medial working length portion  975  is on the order of 8 mm to 28 mm. Second medial working length portion  975  includes porous portion  925  that may be similar to porous portion  725  of balloon  720  as described above with reference to  FIG. 7  and  FIG. 8  and the accompanying text. Porous portion  925  may extend only partially around the circumference of balloon  920  and may extend the entire length of second medial working length portion  975 . A treatment agent delivered through infusion cannula  950  at infusion port  955  may migrate through porous portion  925  of second medial working length portion  975  and be delivered to a vulnerable plaque.  
         [0053]     To locate a vulnerable plaque within a blood vessel, various imaging techniques may be used. Such imaging techniques include intraluminal techniques such as OCT and IVUS. Once a treatment site including a vulnerable plaque has been identified, a catheter assembly, such as the catheter assembly described with reference to  FIG. 4 ,  FIG. 5  and  FIG. 6  or  FIG. 4 ,  FIG. 7  and  FIG. 8  or  FIG. 4  and  FIG. 9  may be introduced into the blood vessel.  
         [0054]      FIG. 10  shows a cross-sectional side view of a blood vessel having a vulnerable plaque therein and a treatment device within the blood vessel. Representatively, treatment device  400 , as described above with reference to  FIG. 4 ,  FIG. 5  and  FIG. 6 , includes balloon  520  that occludes blood vessel  1000  at a point proximal to the treatment site, or proximal to vulnerable plaque  1060 . A treatment agent is then infused into blood vessel  1000  through dispensing port  555  at a point distal to balloon  520 . The treatment agent migrates or diffuses through the thin fibrous cap of vulnerable plaque  1060  to modify the core.  
         [0055]      FIG. 11  shows a cross-sectional side view of a blood vessel having a vulnerable plaque therein and another embodiment of a treatment device disposed in the blood vessel. In this embodiment, treatment device  400  is, for example, a catheter assembly similar to the assembly described above with reference to  FIG. 4 ,  FIG. 7  and  FIG. 8  and the accompanying text. Treatment device  410  includes balloon  720 . Balloon  720  is shown in an inflated state within blood vessel  1100 . Balloon  720  is positioned, in this embodiment, with a working length, at a treatment site including vulnerable plaque  1160 . In one embodiment, balloon  720  is inflated at a low pressure (such as below four atmospheres or even below one atmosphere) and a controlled rate. In one embodiment, balloon  720  is inflated to a diameter that is less than an interior diameter of vulnerable plaque  1160  and preferably does not contact vulnerable plaque  1160 .  
         [0056]     In this embodiment, balloon  720  includes porous portion  725  along the working length of balloon  720 . Infusion port  755  of, for example, an infusion cannula  755  is located within balloon  720 . A treatment agent is introduced through infusion port  755 . The treatment agent will migrate through the porous portion of balloon  720  and may migrate or diffuse into vulnerable plaque  1060 .  
         [0057]     Where porous portion  725  of balloon  720  extends around less than the entire circumference and/or extends less than the working length of balloon  720 , it may be desirable to align (position) the porous portion at vulnerable plaque  1160 . One technique for such aligning or positioning includes placement of an imaging device, such as an OCT device through a guidewire cannula of catheter assembly  400 . Vulnerable plaque  1160  may be identified with the imaging device and balloon  720  rotated or positioned proximally or distally so that porous portion  725  of balloon  720  aligns with (is positioned on or at) vulnerable plaque  1160 .  
         [0058]      FIG. 12  shows a cross-sectional side view of a blood vessel having a vulnerable plaque therein and a treatment device within the blood vessel. Representatively, treatment device  400 , as described above with reference to  FIG. 4  and  FIG. 9 , includes balloon  920  including first medial working length portion  974  and second medial working length portion  975 . Second medial working length portion  975  is placed along a vulnerable plaque and first medial working length portion is located proximally adjacent vulnerable plaque  1260 . Balloon  920  is inflated with a treatment agent delivered through infusion port  955  of infusion cannula  950 . First medial working length elastic portion  974  inflates to contact an inner wall of blood vessel  1200  or to block blood flow, while second medial working length portion  975  of balloon  920  will not significantly inflate at least not significantly enough to come in contact with or damage vulnerable plaque  1260 . A treatment agent introduced through infusion port  955  will migrate through porous portion  925  of balloon  920  and may migrate or diffuse into vulnerable plaque  1260 .  
         [0059]     In another embodiment, the migration or diffusion of a treatment agent into a vulnerable plaque, for example, according to the embodiments described in  FIG. 11  and  FIG. 12  may be assisted. Representative assist techniques include, but are not limited to, electrotransport techniques. For example, a piezoelectric microchip under/on balloon  720 , with a selected frequency, amplitude, duty cycle, and waveform will emit ultrasonic frequency around the detected of vulnerable plaque surface of an arterial wall to facilitate the diffusion of treatment agent into a vulnerable plaque. Another way to facilitate the diffusion of treatment agent into a vulnerable plaque is through iontophoresis, such as by employing a silver/silver chloride electrode under a porous balloon. An electrical potential may be created within the balloon to drive treatment agent out of the balloon and into the vulnerable plaque.  
         [0060]     In the above embodiments, devices and techniques for externally introducing a treatment agent into a vulnerable plaque are described. It is appreciated that the treatment agents may be introduced in various other means. Representatively, a treatment agent may be injected into the vulnerable plaque using, for example, a needle catheter. Concern in this case may be with rupturing the vulnerable plaque with the injection. Possible techniques for minimizing such rupture include supporting the vulnerable plaque with a balloon or stent during injection.  
         [0061]     In the preceding detailed description, reference is made to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the following claims. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.