US20080058758A1

Movatterモバイル変換

Info

Publication number: US20080058758A1
Application number: US11/842,999
Authority: US
Inventors: Arun Ranchod; David M. Griffiths; Alan D. Hirschman
Original assignee: Medrad Inc
Current assignee: Bayer Medical Care Inc
Priority date: 2006-08-31
Filing date: 2007-08-22
Publication date: 2008-03-06
Also published as: US20080097339A1; US8876754B2

Abstract

In one form, the therapeutic agent delivery apparatus is used for infusing a therapeutic agent into a body lumen and includes a lumenal body defining a plurality of infusion ports for infusing the therapeutic agent into the body lumen, and a sensing element distal of the infusion ports and adapted to sense the amount of infused therapeutic agent or any compound derived from the therapeutic agent in the body lumen. In another form, the apparatus includes a lumenal body defining a plurality of infusion ports for infusing the therapeutic agent into the body lumen, and a filtration element distal of the infusion ports and adapted to deliver a reaction agent adapted to react with the therapeutic agent in the body lumen. A sensing element may be provided distal of the filtration element for sensing the amount of infused therapeutic agent or compounds derived therefrom in the body lumen.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of application Ser. No. 11/469,054, filed on Aug. 31, 2006, the contents of which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The field of endeavor relates generally to medical devices and methods. More particularly, the field of endeavor relates to medical devices and methods for infusing therapeutic agents into a body lumen, such as a blood vessel, for treating disorders or conditions present in the body lumen, such as dissolving and disrupting occlusive materials from the blood vessel wall.

2. Description of Related Art

Thrombosis and atherosclerosis are common ailments which occur in humans and which result from the deposition of thrombus within the lumen of blood vessels. When hardened, such deposits are commonly referred to as plaque or clots. Such deposits are common in the peripheral blood vessels that feed the limbs of the human body and the coronary arteries which feed the heart. Stasis, incompetent valves, and trauma in the venous circulation can cause thrombosis, particularly occurring as a deep vein thrombosis in the peripheral vasculature. When such deposits accumulate in localized regions of the blood vessel, they can restrict blood flow and cause a serious health risk. Thrombosis can develop in cerebral vessels, as well, and be the source of ischemic strokes.

In addition to forming in the natural vasculature, thrombosis is a serious problem in “artificial” blood vessels, particularly in peripheral femoral-popliteal and coronary bypass grafts and dialysis access grafts and fistulas. The creation of such artificial blood vessels requires anastomotic attachment at least one, and usually at least two, locations in the vasculature. Such sites of an anastomotic attachment are particularly susceptible to thrombus formation due to narrowing caused by intimal hyperplasia, and thrombus formation at these sites is a frequent cause of failure of the implanted graft or fistula. The arterio-venous grafts and fistulas which are used for dialysis access are significantly compromised by thrombosis at the sites of anastomotic attachment and elsewhere. Thrombosis often occurs to such an extent that the graft needs to be replaced within a few years or, in the worst cases, a few months.

A variety of methods have been developed for treating thrombosis and atherosclerosis in the coronary and peripheral vasculature as well as in implanted grafts and fistulas. Such techniques include surgical procedures, such as coronary artery bypass grafting, and minimally invasive procedures, such as angioplasty, atherectomy, thrombectomy, thrombolysis, transmyocardial revasculaturization, and the like.

A variety of techniques have been developed for dissolving clots using thrombolytic agents, such as tissue plasminogen activator (tPA), streptokinase, urokinase, and the like. Thrombolytic agents can be very effective at attacking and dissolving relatively soft clots, such as that formed in deep veins. Such agents, however, require time to act, and local delivery catheters often employ isolation balloons to provide high local concentrations of the active thrombolytic agents. Even with such enhanced concentrations, the agents can take extended periods to act, rendering the treatments lengthy and inefficient. In some instances, extensive regions of clot simply cannot be effectively treated using thrombolytic agents alone. In such cases, it has been further proposed to provide a mechanical element to disrupt the clot while the thrombolytic agents are being delivered. An example of such a mechanical approach is disclosed, for example, in U.S. Pat. No. 5,947,985 to Mir A. Imran which describes a catheter having axially spaced-apart balloons for isolating a treatment region within a blood vessel. The catheter also includes a port for delivering thrombolytic agent between the spaced-apart balloons and a helical wire for removing clot material from the blood vessel wall to assist in aspiration.

As will be appreciated from the foregoing, it is known that because of blood flow through blood vessels, drugs and therapeutic agents delivered to the site of an angioplasty procedure, for example, can be rapidly dissipated and removed from the delivery site before they can be absorbed in sufficient quantities to become effective. Catheters have therefore been developed to directly deliver drugs to the desired site and maintain the drugs there. In some cases, the treatment catheter includes delivery ports or other structures that bear against the occluded site within the blood vessel and conduct a thrombolytic agent directly to the occluded site as disclosed in U.S. Pat. No. 5,904,670 to Schreiner. U.S. Pat. No. 6,280,413 to Clark et al. discloses a thrombolytic agent and drug delivery catheter with an expanding portion which is adapted to bear against and deliver the thrombolytic agent directly to the occluded site.

U.S. Pat. No. 5,087,244 to Wolinsky et al. discloses a catheter with a flexible balloon having a plurality of minute openings. The balloon can be inflated by heparin. As the wall of the balloon contacts the arterial wall, the heparin exits the balloon, directly on the walls. However, the balloon can block the perfusion of blood distal to the delivery site, depriving downstream tissue of needed blood. This limits the amount of time available for drug delivery. The inflation of the balloon can also damage the arterial wall, promoting restenosis. In addition, since the balloon is inflated by the heparin, heparin can leak out before the arterial wall is contacted, wasting the drug. The balloon further needs to be deflated prior to removal or to allow blood flow. The pressure required to deflate the balloon could also draw blood into the balloon, preventing further use of the catheter until the blood has been removed. U.S. Pat. No. 4,824,436, also to Wolinsky, discloses a drug delivery catheter comprising a pair of occlusion balloons for securing the catheter in position and isolating a region of the artery which has been opened by percutaneous translumenal coronary angioplasty (PTCA), and a drug delivery conduit for delivering heparin under pressure into the region isolated by the occlusion balloons. The pressure of the heparin forces the heparin to coat and penetrate the arterial tissue. This configuration presents similar perfusion problems to those discussed previously in connection with U.S. Pat. No. 5,087,244 to Wolinsky et al. The heparin, therefore, is only delivered for about 5-60 seconds which may be inadequate for sufficient absorption. U.S. Pat. No. 5,336,178 to Kaplan et al. discloses a catheter with drug delivery ribs which are brought into contact with the walls of the blood vessel lumen by an inflatable balloon. A series of ports in the catheter shaft are provided proximal to the balloon to allow for perfusion of blood through the catheter shaft.

Due to the possibility of damaging the blood vessel wall, other devices (i.e., catheters) combine the ability to deliver or infuse a thrombolytic agent with simple agitation within the blood vessel to remove the thrombus and thus avoid inflatable balloon type delivery systems. U.S. Pat. No. 6,663,613 to Evans et al. discloses a catheter which combines the ability to deliver or infuse a thrombolytic agent into a blood vessel with an agitation action which mechanically disrupts the clot forming the occlusion in the blood vessel. Another patent, U.S. Pat. No. 6,939,025 to Evans et al., combines the delivery of a lysing agent to a blood vessel with a low frequency vibration motion of the catheter body to achieve clot dislocation/disruption.

It is well-known that if a portion of the thrombus separates from the blood vessel wall and is transported through the cardiovascular system, it can cause an embolism, or blockage of a blood vessel. A thrombus in a deep vein in the leg can cause a pulmonary embolism. A thrombus in a coronary artery can cause myocardial infarction. Similarly, a thrombus in a cerebral artery can cause cerebral infarction (i.e., ischemic stroke). As a result, devices have been developed which attempt to filter dislodged thrombus or thrombotic material during therapeutic procedures such as the delivery of thrombolytic agents to a blood vessel to minimize the chance of a dislodged thrombus causing significant damage to the patient. A typical form of these devices is as a filter “net” which intercepts the dislodged thrombus or thrombotic material is disclosed in U.S. Pat. No. 6,053,932 to Daniel et al. which discloses an emboli capturing system adapted to catch emboli in blood vessels. This patent discloses a microporous mesh formed of woven or braided fibers or wires, or a microporous membrane, for capturing the dislodged emboli/thrombus. Another such filter “net” is disclosed in U.S. Patent Application Publication No. 2003/0199819 to Beck, which discloses a balloon catheter with downstream “safety net” that prevents any dislodged material from migrating through a patient's bloodstream. Often, “net” type devices are used in combination with a catheter having a suction capability such that dislodged thrombus is sucked into a lumen in the catheter with the mesh or net structure provided mainly for redundant safety purposes. Such a catheter having suction capability is disclosed in U.S. Pat. No. 6,805,692 to Muni et al. One known catheter apparatus includes multiple infusion ports for delivering a thrombolytic agent to a blood vessel with several of the infusion ports provided within a filter basket for delivering the thrombolytic agent in the area defined by the filter basket to dissolve any dislodged thrombus trapped in the filter, (See U.S. Pat. Nos. 6,755,813 and 6,749,619 to Ouriel et al.).

Catheters are also known in the medical field for sensing and providing feedback data relating to physiological data concerning the patient. For example, U.S. Pat. No. 4,552,127 to Schiff discloses a balloon catheter with a stylet having a distal end coupled to an EKG electrode. The stylet extends through the catheter body to couple the EKG electrode to a proximal end of the catheter body and, thus, to the exterior of the patient's body. U.S. Pat. No. 6,319,242 to Patterson et al. discloses a catheter device with a proximity sensor to alert the user/operator of the location of the distal end of the catheter and its proximity to a stent implanted in a blood vessel wall. U.S. Pat. No. 6,682,508 to Meythaler et al. discloses a central nervous system catheter assembly comprising multiple lumens including a drug delivery branch and a monitoring/sensing branch. The monitoring/sensing branch is adapted for sensing and providing feedback information related to intracranial pressure. U.S. Patent Application Publication No. 2004/0167385 to Rioux et al. discloses a catheter with a sensor adapted to measure one or more physiological parameters associated with the status of a blood vessel, including: pressure, flow rate, temperature, fluid velocity, physical dimensions, vessel compliance, pH saline content, gas content, etc.

SUMMARY OF THE INVENTION

Based on the foregoing, it would be desirable to provide improved apparatus and methods for infusing therapeutic agents into a body lumen, such as a blood vessel, for treating disorders or conditions present in the body lumen, such as dissolving and disrupting occlusive materials from the blood vessel wall and further be able to neutralize the harmful effects of the infused agent. It would further be desirable to provide apparatus and methods which can enhance the delivery of thrombolytic agents to a region of a blood vessel wall where thrombus or an occlusion in the form of a clot is present without inhibiting natural blood flow to a significant degree.

In one form, the therapeutic agent delivery apparatus is used for infusing a therapeutic agent into a body lumen and comprises a lumenal body defining at least one and optionally a plurality of infusion ports for infusing the therapeutic agent into the body lumen, and a sensing element distal of the at least one/plurality of infusion ports and adapted to sense the amount, for example concentration, of infused therapeutic agent or any compound derived from the therapeutic agent in the body lumen.

A feedback component may be associated with the sensing element and adapted to provide a sensing element signal to a location outside of the body lumen. The feedback component may provide the sensing element signal to a user interface, for example, connected to a proximal end of the lumenal body. The sensing element signal may be represented to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of the audible, visual, and tactile stimuli. The sensing element signal may be proportional to the amount, for example concentration, of therapeutic agent or derivative thereof sensed by the sensing element.

The sensing element may be adapted to sense the amount, for example concentration, of therapeutic agent or derivative thereof by one or more of resonant mass detection, light reflectance, and electrical conductivity changes. Sensing element may further be adapted to sense the amount, for example concentration, of therapeutic agent via thermal detection principles such as injecting the therapeutic agent at a temperature higher or lower than human body temperature and measuring thermal changes in the physiological fluid in the body lumen. Ion selective electrodes may also be used as part of sensing element or as sensing element itself. The sensing element may be shaped to correspond to the cross-sectional shape of the body lumen, for example, a generally circular shape that stretches across or fills the body lumen.

The sensing element may be formed as a fine wire mesh, for example, and adapted to intercept at least some of the therapeutic agent or derivative thereof in the body lumen. Additionally, the sensing element may be formed of electrically conductive material, for example, in the form of a fine wire mesh. The electrically conductive material may change conductivity when exposed to the therapeutic agent or derivative thereof.

A filtration element may be disposed distal of the at least one infusion port and proximal of the sensing element. Such a filtration element may comprise tree-like/shaped filtration structures. A second, inner lumenal body may be coaxial with the lumenal body and comprise a portion proximal of the sensing element defining at least one distal infusion port for infusing the therapeutic agent, a different therapeutic agent, or a reaction agent adapted to react with the therapeutic agent into the body lumen.

In another form, the apparatus includes a lumenal body defining at least one and optionally a plurality of infusion ports for infusing the therapeutic agent into the body lumen, and a filtration element distal of the infusion ports and adapted to deliver a reaction agent adapted to react with the therapeutic agent in the body lumen.

In one embodiment, the filtration element may be coated with the reaction agent. In another embodiment, the filtration element may comprise a plurality of generally tree-shaped structures which are, for example, coated with the reaction agent. In a further embodiment, the filtration element may be in the form of at least one distal infusion port disposed distal or downstream of the lumenal body for infusing the reaction agent into the body lumen. Moreover, a sensing element may be provided distal or downstream of the at least one distal infusion port.

A sensing element may be provided distal of the filtration element. The sensing element is adapted to sense the amount, for example concentration, of infused therapeutic agent or any compound derived from the therapeutic agent in response to the reaction agent in the body lumen. A feedback component may be associated with the sensing element. The feedback component may be adapted to provide a sensing element signal to a location outside of the body lumen. The feedback component may provide the sensing element signal to a user interface, for example, connected to a proximal end of the lumenal body. The sensing element signal may be represented to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of an audible, visual, and tactile stimuli. The sensing element signal may be proportional to the amount, for example concentration, of therapeutic agent or derivative thereof sensed by the sensing element.

The sensing element may be adapted to sense the amount, for example concentration, of therapeutic agent or derivative thereof by one or more of resonant mass detection, light reflectance, and electrical conductivity changes. The sensing element may be shaped to correspond to the cross-sectional shape of the body lumen, for example, a generally circular shape that stretches across or fills the body lumen.

A further aspect relates to a sensing element for use with a lumenal body used to deliver a therapeutic agent to a body lumen. The sensing element generally comprises an electrically conductive body structure adapted to change conductivity when exposed to the therapeutic agent or any compound derived from the therapeutic agent. The body of the sensing element may be in the form of an electrically conductive fine wire mesh. The body of the sensing element may also be shaped to correspond to the cross-sectional shape of the body lumen, for example, a generally circular shape that stretches across or fills the body lumen. The sensing element may comprise a feedback component adapted to provide a sensing element signal to a location outside of the body lumen. The sensing element may optionally include a user interface coupled to the feedback component for receiving the sensing element signal. Such a user interface may be adapted to represent the sensing element signal to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of the audible, visual, and tactile stimuli. The sensing element signal may be proportional to the amount, for example concentration, of therapeutic agent or derivative thereof sensed by the sensing element. The sensing element may be adapted to sense a combination of a therapeutic agent and a reaction agent adapted to react with the therapeutic agent

Another aspect relates to a filtration element for use with a lumenal body used to deliver a therapeutic agent to a body lumen. The filtration element may comprise a plurality of structures coated with a reaction agent adapted to react with the therapeutic agent. Such filtration structures may be coated structures that are generally tree-shaped in configuration.

A method of infusing a therapeutic agent into a body lumen using the therapeutic agent delivery apparatus is also an concept described herein. In one embodiment, the method comprises inserting a lumenal body into the body lumen, the lumenal body defining at least one infusion port for infusing the therapeutic agent into the body lumen; infusing the therapeutic agent into the body lumen; and sensing the amount, for example concentration, of infused therapeutic agent or any compound derived from the therapeutic agent in the body lumen with a sensing element disposed distal of the at least one infusion port.

The method may comprise providing a sensing element signal to a location outside the body lumen with a feedback component associated with the sensing element. Such a sensing element signal may be provided to a user interface, for example, connected to a proximal end of the lumenal body. The sensing element signal may be represented to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of the audible, visual, and tactile stimuli. The sensing element signal may be proportional to the amount, for example concentration, of therapeutic agent or derivative thereof sensed by the sensing element. In one form, the sensing element is adapted to sense the amount, for example concentration, of therapeutic agent or derivative thereof by one or more of resonant mass detection, light detection, and electrical conductivity changes.

An aspect of the method may comprise intercepting at least some of the therapeutic agent or derivative thereof in the body lumen with the sensing element. Another aspect of the method may comprise infusing additional therapeutic agent, a different therapeutic agent, or a reaction agent adapted to react with the therapeutic agents into the body lumen through at least one distal infusion port proximal of the sensing element. A further aspect may comprise filtering the therapeutic agent or derivative thereof in the body lumen with a filtration element disposed distal of the infusion ports and proximal of the sensing element.

Another embodiment of the method of infusing a therapeutic agent into a body lumen generally comprises inserting a lumenal body into the body lumen, the lumenal body defining at least one infusion port for infusing the therapeutic agent into the body lumen; infusing the therapeutic agent into the body lumen; and delivering a reaction agent adapted to react with the therapeutic agent in the body lumen with a filtration element disposed distal of the at least one infusion port. The reaction agent may be coated on the filtration element and filtering of the therapeutic agent occurs by contact between the coated filtration element and the therapeutic agent.

The reaction agent may be delivered by infusing the reaction agent through at least one distal infusion port forming the filtration element. The method may comprise sensing the amount, for example concentration, of infused therapeutic agent or any compound derived from the therapeutic agent in response to the reaction agent in the body lumen with a sensing element disposed distal of the at least on distal infusion port.

Additionally, the method may comprise sensing the amount, for example concentration, of infused therapeutic agent or any compound derived from the therapeutic agent in response to the reaction agent in the body lumen with a sensing element disposed distal of the filtration element. A sensing element signal may be provided to a location outside the body lumen with a feedback component associated with the sensing element. As an example, the sensing element signal may be provided to a user interface, for example, connected to a proximal end of the lumenal body. The sensing element signal may be represented to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of the audible, visual, and tactile stimuli. The sensing element signal may be proportional to the amount, for example concentration, of therapeutic agent or derivative thereof sensed by the sensing element. The sensing element may sense the amount, for example concentration, of therapeutic agent or derivative thereof by one or more of resonant mass detection, light reflectance, and electrical conductivity changes. An aspect of the method may comprise intercepting at least some of the therapeutic agent or derivative thereof in the body lumen with the sensing element.

Further details and advantages will become clear upon reading the following detailed description in conjunction with the accompanying drawing figures, wherein like parts are identified with like reference numerals throughout.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an embodiment of an intralumenal catheter system including a control device and an optional auxiliary display device.

FIG. 2 is a longitudinal cross-sectional view of a distal end portion of the catheter ofFIG. 1 shown indwelling in a blood vessel requiring treatment.

FIG. 3 is a longitudinal cross-sectional view of the distal end portion of the catheter ofFIG. 2 and showing a filtration element in a partially deployed state and a sensing element in a fully deployed state.

FIG. 4 is a longitudinal cross-sectional view of the of the distal end portion of the catheter ofFIG. 2 showing the filtration element and sensing element each in a fully deployed state.

FIG. 5 is a perspective view of the distal end portion of the catheter ofFIG. 1 showing the filtration element and sensing element each in a fully deployed state.

FIG. 6 is a perspective view of a portion of the distal end portion of the catheter ofFIG. 5 showing operational aspects of the sensing element.

FIG. 7 is a longitudinal cross-sectional view of a proximal end portion of the catheter ofFIG. 1.

FIG. 8 is a longitudinal cross-sectional view of the distal end portion of the catheter ofFIG. 2 showing the delivery of a therapeutic agent within the confines of the blood vessel to treat a thrombus in the blood vessel.

FIG. 9A is a longitudinal cross-sectional view of the distal end portion of the catheter ofFIG. 2 showing operation of the catheter in one mode and the results of the delivered therapeutic agent on the thrombus.

FIG. 9B is schematic view of the operation of the catheter in the mode depicted inFIG. 9A.

FIG. 10A is a longitudinal cross-sectional view of the distal end portion of the catheter ofFIG. 2 showing operation of the catheter in another mode and the results of the delivered therapeutic agent on the thrombus.

FIG. 10B is schematic view of the operation of the catheter in the mode depicted inFIG. 10A.

FIG. 11A is a longitudinal cross-sectional view of the distal end portion of the catheter ofFIG. 2 showing operation of the catheter in a third mode and the results of the delivered therapeutic agent on the thrombus.

FIG. 11B is schematic view of the operation of the catheter in the mode depicted inFIG. 11A.

FIG. 12 is a longitudinal cross-sectional view of the catheter ofFIG. 1 according to another embodiment.

FIG. 13 is a longitudinal cross-sectional view of the alternative catheter embodiment ofFIG. 12 showing operation of the catheter and the results of the delivered therapeutic agent on the thrombus.

FIG. 14 is a longitudinal cross-sectional view of the catheter ofFIG. 1 according to a third embodiment.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

For purposes of the description hereinafter, spatial orientation terms, if used, shall relate to the referenced embodiment as it is oriented in the accompanying drawing figures or otherwise described in the following detailed description. However, it is to be understood that the embodiments described hereinafter may assume many alternative variations and configurations. It is also to be understood that the specific devices illustrated in the accompanying drawing figures and described herein are simply exemplary and should not be considered as limiting.

A general aspect described herein relates to an apparatus and method for providing a therapeutic substance such as a therapeutic agent or drug or, typically in liquid form, to a body lumen for treating a disorder or condition present in the body lumen and thereafter removing or intercepting the substance and/or neutralizing or rendering inert any harmful aspects of the therapeutic substance to prevent damage to healthy tissue in the body lumen and/or limit or eliminate or minimize any possible harmful effects to downstream tissues and organs. The body lumen may be a blood vessel such as an artery in which atherosclerosis is present, which is the result of the deposition of occluding deposits within the lumen of the blood vessel. When hardened, such deposits or “thrombus” are commonly referred to as plaque, clots, or occlusions. Other lumens or cavities or body regions which may be treated by the apparatus and method described herein include the urethra, bladder, prostate, rectum, bile duct, pancreatic duct and central nervous system, such as along the spinal column, as examples. Drugs or other therapeutic agents may be provided conceivably to any body lumen or cavity to treat a variety of disorders or conditions in the body lumen using the physical structures and methods described herein. Accordingly, the foregoing listing of lumens/cavities is not intended to be exhaustive. Hereinafter, “therapeutic agent” is intended to be a term encompassing any substance intended to treat a disorder or condition present in a body lumen or cavity. Two specific therapeutic agents, thrombolytic agent for treating thrombus present in a blood vessel and doxorubicin for treating cancerous tumors, will be discussed in this disclosure as a vehicle to describe structural and operational aspects of the apparatus and methods. However, these two specific therapeutic agents are not intended to be limiting and are cited for exemplary purposes only.

In one embodiment, the apparatus is an intralumenal catheter adapted to provide a therapeutic agent to a body lumen such as a blood vessel to treat a disorder or condition present in the body lumen such as a thrombus which causes atherosclerosis in the blood vessel. As an example, the catheter provides the therapeutic agent to treat the thrombus at or near the location of the thrombus in the blood vessel. A feature of the catheter relates to using the natural flow of physiological fluid in the body lumen, in the present case blood flowing in a blood vessel, so that the therapeutic agent is transported by action of the natural flow of fluid. Accordingly, the therapeutic agent may be carried by the natural flow of fluid from the catheter to the treatment site and possibly beyond the treatment site. The carrying of therapeutic agent by a naturally occurring physiological fluid stream may be termed natural or passive fluid transport.

Another feature of the catheter relates to a filtration apparatus or element being located at a distal or downstream location from the location of therapeutic agent infusion which is used to intercept and inhibit the harmful effects of the therapeutic agent with mechanical and/or chemical filtration features or elements. For example, it is known that some therapeutic agents, such as tissue plasminogen activator (tPA) used as a thrombolytic agent and doxorubicin for treating cancerous tumors, can have adverse effects on healthy body tissue and/or generally cause negative downstream effects. Accordingly, it is desirable to localize the application of such therapeutic agents to the affected area within the body lumen. The distal filtration element may use a combination of mechanical filtration structure(s) and chemical filtration to filter and/or render inert or harmless via chemical reaction the infused therapeutic agent to substantially “remove” the infused agent or in effect substantially remove the harmful consequences of the therapeutic agent on the body lumen. As indicated previously, the natural flow of physiological fluid in the body lumen may be used to passively transport the therapeutic agent to the filtration element where the therapeutic agent naturally “washes” over the filtration element which mechanically and/or chemically substantially removes or renders substantially harmless or inert the deleterious effects of the therapeutic agent. Typically, such passive chemical filtration occurs by a chemical reaction between the therapeutic agent and another substance adapted to react with the therapeutic agent (i.e., a reaction agent) to render substantially harmless the deleterious effects of the therapeutic agent. Such a substance may be referred to as a “neutralizing” or “inhibiting” or “reaction” agent and these terms may be used interchangeably herein. However, “reaction agent” is generally used herein as a term used to described any substance which reacts with the therapeutic agent in manner that renders the therapeutic agent harmless or transformed for other purposes, such as to facilitate sensing of chemical compounds in the body lumen. Moreover, the neutralizing or inhibiting or reaction agent may be adapted to bind to the therapeutic agent thereby trapping the therapeutic agent in the mechanical filtration structures. It will be appreciated that the neutralizing or inhibiting or reaction agent may be delivered in liquid form to chemically react with the therapeutic agent but could also be part of the mechanical filtration structures such a solid or liquid coating on the structure or structures. The mechanical filtration structures may further be a biomaterial with an interfacial layer or portion adapted to chemically react with the therapeutic agent, for example, to cause the therapeutic agent to bind to the mechanical filtration structures. In such a situation, mechanical and chemical filtration may be accomplished by the same structure or structures.

Another feature of the catheter relates to a sensing apparatus or element being located distal or downstream of the filtration element which is used to sense the amount, typically concentration, of therapeutic agent remaining in the body lumen and/or a compound derived from the chemical reaction between the therapeutic agent and the neutralizing or inhibiting agent or reaction agent discussed previously. The sensing element senses the therapeutic agent and/or derived compound and provides a signal indicative of the amount of therapeutic agent remaining or neutralized in the body lumen downstream of the filtration element. This signal may then be used to quantify the amount of therapeutic agent remaining in the body lumen such as a blood vessel and, further, be displayed to the operator of the catheter. The signal may be displayed or communicated to the catheter operator to provide real-time or near real-time quantitative information regarding the amount of therapeutic agent injected, remaining in the body lumen, and/or neutralized. If desired, a specific agent or substance may be provided as part of the chemical filtration feature of the filtration element to chemically react with the therapeutic agent and, for example, bind with the therapeutic agent. This combined or derived chemical substance may be adapted to interact with the sensing element to cause a specific response, for example a signal, to be communicated by the sensing element to the operator. As an example, the derived or combined substance may have a component that is specifically adapted to interact with the sensing element to elicit a signal from the sensing element which represents the amount of therapeutic agent injected, remaining in the body lumen, and/or neutralized. Communication to the operator may be by visual, audible, tactile, or a combination of visual, audible, and tactile conveyances. For example, the sensing element signal may be communicated via wires or wirelessly to a control device or a display device or other user interface which visually alerts or displays information regarding the amount of therapeutic agent injected, remaining in the body lumen, and/or neutralized. The display may, for example, be part of a computer or other control device. Such a device may include a mechanism to audibly convey the information to the operator and/or a tactile device, such as a hand-held device, to convey the information to the operator tactilely. Specific examples of conveyances for providing feedback to the catheter operator are detailed herein. Moreover, the signal may also be used as a basis or input to the control device which can warn of an unsafe condition like an excessive amount of therapeutic agent concentration in the body lumen, and the control device may use this information to control, for example reduce the amount of therapeutic agent delivered, or cease delivery altogether of the therapeutic agent.

With the foregoing introduction in mind, one embodiment is an apparatus and method for performing thrombolysis in a body lumen and, more particularly, as an apparatus and method for delivering an infusate in the form of a thrombolytic agent into a blood vessel to dissolve thrombus causing atherosclerosis in the blood vessel. Referring initially toFIGS. 1-6, such as an infusate-delivering device is anintralumenal catheter apparatus10 for delivering an infusate, thrombolytic agent in this example, into ablood vessel12 to dissolvethrombus14 present in theblood vessel12. As an example,thrombus14 may be present in acerebral blood vessel12 and such athrombus14 has the potential of causing an ischemic stroke. Typically, ischemic strokes occur in the middle cerebral artery and, in the present embodiment,catheter10 is sized to pass into the middle cerebral artery to deliver a therapeutic agent for dissolvingthrombus14. Accordingly,catheter10 is a 3 or 4 French (Fr) catheter when used for this specific application. However,catheter10 may be of a larger size to fit into larger blood vessels such as a 5 Fr catheter and larger.

As indicated previously, the exemplary structure and operation ofcatheter10 will be described withcatheter10 delivering a thrombolytic agent “A”, such as plasmin, tissue plasminogen activator (tPA), streptokinase, urokinase, and the like toblood vessel12 to treatthrombus14. Other known thrombolytic agents A include alteplase, reteplase, tenecteplase, staphylokinase, and desmoteplase. However, these specific thrombolytic agents should not be considered as an exhaustive listing, andcatheter10 is suited to delivering a number of therapeutic agents toblood vessel12 to treatthrombus14 or for treating other abnormalities and conditions inblood vessel12 or for other purposes. It is generally known that thrombolytic agents such as plasmin, tPA, and the like can damage healthy arterial tissue, downstream organs and tissue, and, in the present circumstance, an oversupplying of thrombolytic agent A incerebral blood vessel12 may act upon “downstream” thrombus (not shown) resulting in dislodging of the thrombus or pieces thereof which could be responsible for inducing ischemic strokes. A feature of thecatheter10 relates to a filtration apparatus or element being located at a distal or downstream location from where the thrombolytic agent A is delivered toblood vessel12. This filtration element as described herein is used to intercept the thrombolytic agent A with mechanical and/or chemical filtration and neutralize or inhibit the harmful effects of the thrombolytic agent A. This filtration element or structure, described in detail herein, is provided as part ofcatheter10 and is used to mechanically filter and/or chemically neutralize or render inert injected or infused thrombolytic agent A to prevent damage to the non-thrombolized portion ofblood vessel12, downstream tissue and organs, and prevent the dissolution and dislodgement of downstream thrombus which could cause ischemic stroke (in the present circumstance), pulmonary embolism, or coronary embolism.

Thrombus

14 is adhered to aninner surface16 ofblood vessel12 and undesirably restricts blood flow through theblood vessel12, also known as arteriolosclerosis. Additionally,thrombus14 or portions thereof place the patient at risk of ischemic stroke if thethrombus14 or portions thereof break-off frominner surface16 and travel through and become lodged in downstream cerebral blood vessels.Thrombus14 extends along theinner surface16 of theblood vessel12 over an axiallength L. Catheter10 is generally adapted to treatthrombus14 by injecting thrombolytic agent A in the axial region or area defined by length L to dissolve thethrombus14. The direction of natural blood flow in blood vessel is designated byarrow18 in the various drawing figures.

Catheter

10 comprises multiple coaxial catheter assemblies or devices generally divisible into first and second (i.e., outer and inner)

catheters assemblies

20 and70 that extend coaxially along a central longitudinal axis CL ofcatheter10. First orouter catheter20 forms the outer catheter portion ofcatheter10 and is disposed about second orinner catheter70.First catheter20 comprises an innerfluid delivery catheter22 surrounded by an outer sheath orfirst sheath catheter50.Fluid delivery catheter22 is a tubular member formed by alumenal body24 having inner and

outer surfaces

26 and28.Inner surface26 defines afirst lumen30 that extends throughlumenal body24 offluid delivery catheter22. Anend wall32 is provided at adistal end34 oflumenal body24 offluid delivery catheter22 and extends between inner and

outer surfaces

26 and28. Aproximal end36 oflumenal body24 offluid delivery catheter22 is shown inFIG. 7 discussed herein.End wall32 defines adistal opening38 through whichsecond catheter70 projects or extends.End wall32 seals aroundsecond catheter70 to prevent or minimize fluid leakage throughdistal opening38.

Fluid delivery catheter

22 has aninfusion section40 that includes a plurality ofinfusion ports42 defined inlumenal body24 for delivering thrombolytic agent A to the vicinity ofthrombus14.Infusion section40 may have any suitable length as measured fromdistal end34 oflumenal body24 offluid delivery catheter22 to treatthrombus14.Infusion ports42 extend throughfirst lumen30 frominner surface26 toouter surface28 oflumenal body24 and are spaced axially apart. In the illustrated embodiment,infusion ports42 extend axially alonginfusion section40 in a helical pattern but could alternatively extend in another suitable pattern. Another suitable distribution pattern forinfusion ports42 ininfusion section40 is disclosed in U.S. Provisional Patent Application No. 60/520,071, filed Nov. 15, 2003, and PCT Patent Application No. PCT/US2004/038093 (WO 2005/049110) each entitled “Catheter for Diagnostic Imaging and Therapeutic Purposes” and assigned to the same assignee as the present application and are incorporated herein by reference in their entirety. These Applications further disclose suitable size and infusion port “density” distribution information forinfusion ports42. If desired,infusion ports42 may vary in size, for example, increase in diameter towarddistal end34 oflumenal body24 offluid delivery catheter22. Havinginfusion ports42 increase in size from proximal end36 (FIG. 7) towarddistal end34 may provide a more evenly distributed flow pattern throughoutinfusion section40 because the fluid pressure insidefirst lumen30 drops both from frictional losses and from the thrombolytic agent A escaping through the more proximally-locatedinfusion ports42 along the axial length oflumenal body24 offluid delivery catheter22. As an example,infusion ports42 may be adapted to deliver infusate, in this case thrombolytic agent A, at a flow rate of up to 200 cc/hr. However, in the case of tPA as the thrombolytic agent A, delivery rates and treatment amounts are governed by Food and Drug Administration (FDA) regulations.

A firstannular space46 is defined between the inner diameter oflumenal body24 offluid delivery catheter22 and the outer diameter ofsecond catheter70 described herein.Annular space46 permits the flow of thrombolytic agent A throughfirst lumen30 defined bylumenal body24 offluid delivery catheter22 to reachinfusion section40 andinfusion ports42 in particular, and subsequent injection or delivery of the thrombolytic agent A intoblood vessel12 and the region ofblood vessel12 in whichthrombus14 is present. As described further herein in connection withFIG. 7, the thrombolytic agent A is introduced intofirst lumen30 atproximal end36 oflumenal body24 offluid delivery catheter22 and flows throughannular space46 defined in thefirst lumen30 under pressure until reachinginfusion section40 andinfusion ports42.

Outer sheath

50 coaxially surroundsfluid delivery catheter22.Fluid delivery catheter22 andouter sheath50 are axially movable relative to one another.Fluid delivery catheter22 is axially movable relative toouter sheath50 so thatdistal end34 andfluid infusion section40 oflumenal body24 of thefluid delivery catheter22 are projectable or extendable outward fromouter sheath50. However,outer sheath50 may be retractable relative tofluid delivery catheter22 to achieve the same exposed configuration offluid infusion section40 oflumenal body24 offluid delivery catheter22.Outer sheath50 is also a tubular member comprising alumenal body52 having inner and

outer surfaces

54 and56. Anend wall58 is provided at adistal end60 oflumenal body52 ofouter sheath50 and extends between inner and

outer surfaces

Second catheter

70 is coaxially disposed withinfirst catheter20 and comprises a filtering andsensing catheter72 surrounded by an inner sheath orsecond sheath catheter100. Filtering andsensing catheter72 comprises a filtration element ordevice74 and a distally located sensing element ordevice76.Filtration element74 is generally adapted to expand radially outward upon deployment frominner sheath100 and is further generally adapted to filter and trap dislodgedthrombolytic material78 which results when thrombolytic agent A is introduced intoblood vessel12 viafluid delivery catheter22. Additionally,filtration element74 is adapted to mechanically and/or chemically “filter” the thrombolytic agent A as described in further detail herein. Filtering andsensing catheter72 is likewise a tubular member formed by alumenal body80 having inner and

outer surfaces

82,84.Inner surface82 defines asecond lumen86 that extends throughlumenal body80 of filtering andsensing catheter72.Lumenal body80 has adistal end88 and aproximal end90 shown inFIG. 7 discussed herein.Lumenal body80 terminates atdistal end88 with aflexible tip92 which aids in guiding filtering andsensing catheter72 withinblood vessel12 upon deployment frominner sheath100 and first orouter catheter20.Flexible tip92 also enclosessecond lumen86 atdistal end88 oflumenal body80 of filtering andsensing catheter72 to form an enclosed cavity within thelumenal body80.

Inner sheath

As described previously,second catheter70 projects or extends throughdistal opening36 inend wall32

lumenal body

24 offluid delivery catheter22. In particular,end wall32 seals aroundlumenal body102 ofinner sheath100 to prevent or minimize fluid leakage throughdistal opening36. Nonetheless, relative axial movement is permitted by the cooperative engagement oflumenal body102 indistal opening36. As shown inFIGS. 2-4 and7, firstannular space46, as described previously, permits the flow of thrombolytic agent A throughlumen30 defined bylumenal body24 offluid delivery catheter22. This flow passes throughannular space46 to reachinfusion section40 andinfusion ports42 in particular and is subsequently injected or delivered toblood vessel12 and the region ofblood vessel12 in which thethrombus14 is present. Secondannular space116 is optionally defined between the inner diameter oflumenal body102 ofinner sheath100 and the outer diameter oflumenal body80 of the filtering andsensing catheter72.

Filtration element

74 is a radially expandable structure that is disposed aboutlumenal body80 of filtering andsensing catheter72. In one embodiment,filtration element74 is comprised of a plurality of tree-like filtration structures120 (hereinafter filtration structures120) or a similar structure or structures that provide for mechanical filtration offluid flow18 inblood vessel12 and copious surface area for a chemical coating, solid or liquid, with a chemical adapted to react with the thrombolytic agent A. In one instance, the chemical coating may be adapted to neutralize, inhibit, or render harmless the thrombolytic agent A, termed herein a “reaction agent”, and bind the thrombolytic agent A tofiltration structures120, as schematically shown inFIG. 9B discussed herein. In another instance, the chemical coating may be adapted to neutralize, inhibit, or render harmless the thrombolytic agent A and bind the thrombolytic agent A tofiltration structures120 but also include another agent which combines with the thrombolytic agent A and which results in a combined or derived “D” compound that is specifically designed or adapted to be sensed bydownstream sensing element76, as shown schematically inFIG. 10B discussed herein. In a further instance, the chemical coating may possibly be adapted to convert the thrombolytic agent A to a non-harmful state or form and allow this converted or derived compound D to flow passively downstream or distal fromfiltration element74 without binding tofiltration structures120, as shown schematically inFIG. 11B discussed herein. Each of the foregoing alternatives may be described or identified as “passive” chemical filtration discussed previously. Additionally, in each case the natural flow of physiological fluid, in this case blood flow, carries the thrombolytic agent A tofiltration element74 where mechanical and chemical filtration occurs. Mechanical filtration is primarily designed for the dissolved or dislodgedthrombotic material78 while passive chemical filtration is primarily designed for the neutralization or inhibiting of thrombolytic agent A. As an alternative to tree-like mechanical structures,filtration structures120 could be an open-cell layer or structure, such as a sponge-like structure, that maximizes potential surface area for coating and filtration. The tree-shaped orientation or configuration offiltration structures120 is intended to also represent such an open-cell layer or sponge-like structure in the Figures.

Filtration structures

As will be clear from viewingFIGS. 2-4, as filtering andsensing catheter72 is deployed distally frominner sheath100 or, alternatively,inner sheath100 is retracted proximally relative to filtering andsensing catheter72,filtration element74 is exposed from or projects outward from distal opening114 inend wall108 oflumenal body102 ofinner sheath100. Asfiltration element74 is exposed,filtration structures120 begin to deploy as shown inFIG. 3.Filtration structures120 expand radially outward to their memorized shape withstem portions122 defining an acute angle with central longitudinal axis CL ofcatheter10. However,filtration structures120 may form any desirable angle with the central longitudinal axis CL ofcatheter10 and are not limited to an acute angle, although this provides for easy expression offiltration element74 frominner sheath100 and subsequent ingress intoinner sheath100 to enable easy removal ofsecond catheter70 and/orcatheter10 fromblood vessel12.Filtration element74 has a fully expanded condition shown inFIG. 4 in which thefiltration structures120 stretch radially acrossblood vessel12 to filterfluid flow18 inblood vessel12. In the expanded condition,filtration element74 has an inlet orupstream side126 and an outlet ordownstream side128. It will be clear thatfiltration structures120 are disposed around the circumference oflumenal body80 of filtering andsensing catheter72 and, thus, fully encompass 360° of the cross-sectional area ofblood vessel12 to ensure that there is full coverage forthrombotic material78 dissolved and dislodged from theinner surface16 ofblood vessel12.

As described previously, sensingelement76 is disposed distal or downstream offiltration element74. Accordingly, sensingelement76 is in serial relationship and distal to bothinfusion ports42 ininfusion section40 oflumenal body24 offluid delivery catheter22 andfiltration element74. Sensingelement76 in one form, as illustrated, is afine wire mesh130 formed into the shape of a circle, oval, or other such shape that, when deployed, is positioned acrossblood vessel12 and generally matches the cross-sectional shape ofblood vessel12. Sensingelement76 may likewise be made of a flexible solid elastic or superelastic material or a memory metal material which can be preformed into a memorized shape and subsequently deformed into another shape. As withfiltration element74, the expanded or deployed state of sensingelement76 preferably comprises the memorized shape of thesensing element76. Sensingelement76 is adapted to react with any injected thrombolytic agent A remaining in the fluid stream as represented byarrow18 inblood vessel12 after chemical filtration has occurred infiltration element74 or any compound “D” derived from the injected thrombolytic agent A that is left in thefluid flow18 after it has passedfiltration element74. Sensingelement76 is also designed to deliver a response signal indicative of and typically proportional to the amount of injected, active thrombolytic agent A left in thefluid flow18 after it has passedfiltration element74. Sensingelement76 determines the level of remaining thrombolytic agent A by measuring conductivity changes C inwire mesh130 caused by the interception of thrombolytic agent A inwire mesh130.Wire mesh130 is composed of an electrically conductive material of a given resistance. As described previously, when reacting withfiltration element74, the injected thrombolytic agent A desirably binds to the reaction agent onfiltration structures120 thereby chemically trapping or filtering the thrombolytic agent A in thefiltration element74. Any remaining active thrombolytic agent A (seeFIG. 9B) reacts withwire mesh130 which changes the electrical conductivity of thewire mesh130. Conductivity changes, as represented by arrows C inFIG. 6, are communicated to a feedback device orcomponent132, in this case a transmitting wire. Depending on the ratio of the area ofwire mesh130 exhibiting conductivity changes C to the cross section ofblood vessel12, assumingwire mesh130 extends completely across the cross section ofblood vessel12, the total amount of injected thrombolytic agent A in an active state may be determined.

As indicated previously,wire mesh130 formingsensing element76 may be sized such that it fills the entirety of the cross section of theblood vessel12. In this configuration,wire mesh130 may act as an embolus/thrombus catching device as well to prevent the progression ofthrombolytic material78 to a downstream location inblood vessel12. While sensingelement76 was described hereinabove as awire mesh130 that works on the principle of conductivity changes C to sense the level of active or neutralized thrombolytic agent A inblood vessel12 downstream offiltration element74, this specific configuration is not intended to be limiting. Sensingelement76 may operate on a principle of resonant mass detection element (Coriolis flow meter), or on an optical reflectance principle, for example fluoroscopy or spectroscopy, as described herein in connection withFIG. 14. A suitable Coriolis flow meter for use as sensingelement76 and in place ofwire mesh130 is manufactured by Emerson Process Management and sold under the trademark Micro Motion® F-Series Mass Flow and Density Meters. Another suitable mass flow meter for use in place ofwire mesh130 is manufactured by Integrated Sensing Systems, Inc. and sold under the trade name ISSYS micro-density meter. Such mass flow meters are used for chemical and/or biological detection.

Moreover, sensingelement76 may further be adapted to sense the amount of therapeutic agent A via thermal detection principles such as injecting the therapeutic agent A at a temperature higher or lower than human body temperature and measuring thermal changes in the physiological fluid in the body lumen. Ion selective electrodes may also be used as part ofsensing element76 or as sensingelement76 itself, and measure the amount of therapeutic agent A based on ion detection principles.

Feedback component

132 in the illustrated embodiment is a conducting wire which is used as a means to carry/deliver a sensing element signal to the proximal terminus ofcatheter10 or some point nearby which is external to a patient's body. This sensing element signal delivered is proportional to the amount of remaining thrombolytic agent A in an active state sensed by sensingelement76 or the amount of neutralized or inhibited thrombolytic agent A and now in the form of derived compound D from which the amount of active thrombolytic agent A remaining may be determined. In the illustrated embodiment,feedback component132 is a conducting wire that is housed withinsecond lumen86 defined bylumenal body80 of filtering andsensing catheter72 and is desirably not in contact with thelumen body80, and is otherwise protected/encased from outside conductive influences.Feedback component132 terminates at the proximal terminus ofcatheter10 and is connected to acontrol device134 such as a computer and/or adisplay device136 or another similar type user interface device. As shown inFIG. 1,control device134 includes a hand-held control device orcontroller138 which may be used to control operation of catheter, for example, to extend and retract inner orsecond catheter70 relative to outer orfirst catheter20 and vice versa. Additionally, hand-heldcontrol device138 may be used to control the extension and retraction offluid delivery catheter22 relative toouter sheath50 and vice versa, filtering andsensing catheter72 relative toinner sheath50 and vice versa and, if desired,inner sheath100 relative tofluid delivery catheter22 and vice versa.

Referring, in particular, toFIG. 7, a cross-sectional view of aproximal portion140 ofcatheter10 is shown. This view shows control features for the respective first and

second catheter assemblies

20,70 which allow the axial extension or retraction of second orinner catheter assembly70 relative to first orouter catheter assembly20 and vice versa by the operator ofcatheter10. As shown inFIG. 7, afirst collar142 is provided at theproximal end62 oflumenal body52 ofouter sheath50 for manipulatingouter sheath50 relative tolumenal body24 offluid delivery catheter22. Likewise, asecond collar144 is provided at theproximal end36 oflumenal body24 offluid delivery catheter22 for manipulatingfluid delivery catheter22 relative toouter sheath50. Additionally, an infusion lumen orluer146 is provided inlumenal body24 offluid delivery catheter22 to provide thrombolytic agent A tofirst lumen30 defined bylumenal body24 offluid delivery catheter22.Such infusion luer146 may be connected in an infusion pump (not shown) or other device adapted to supply a continuous flow of thrombolytic agent A on demand tofirst lumen30.

As further shown inFIG. 7,inner sheath100 at itsproximal end112 is joined, for example, adhesively to atubular body148 which includes adistal end150 disposed insecond collar144 associated withfluid delivery catheter22. The joint connection betweeninner sheath100 andtubular body148 permitsinner sheath100 to be manipulated relative tofluid delivery catheter22 for extending and retracting inner sheath relative tofluid delivery catheter22. Moreover, theproximal end90 oflumenal body80 of filtering andsensing catheter72 is attached to aplug member152 which is movably disposed within acentral passage154 intubular body148.Plug member152 permits the axial movement of filtering andsensing catheter72 withininner sheath100. InFIG. 7, it will be appreciated that each of thefluid delivery catheter22,outer sheath50, filtering andsensing catheter72, andinner sheath100 are extended to their substantially distal-most position resulting generally in the configuration of catheter elements shown inFIG. 4, for example. O-rings, as illustrated, may be provided between theproximal end62 oflumenal body52 ofouter sheath50 andlumenal body24 offluid delivery catheter22, and between theproximal end36 oflumenal body24 and thelumenal body102 ofinner sheath100 to prevent thrombolytic agent A from leaking from theproximal portion140 ofcatheter10. Further,FIG. 7 illustrates thatlumenal body80 of filtering andsensing catheter72 may extend through and outward fromplug member152 and continue to enclosefeedback component132 through to connection to controldevice134 and/ordisplay device136.

Referring additionally toFIGS. 8-11, exemplary use ofcatheter10 in performing thrombolysis onthrombus14 will now be described. Prior to usingcatheter10 to perform thrombolysis, a medical practitioner may elect to determine the size ofthrombus14 inblood vessel12 using known cardio-vascular imaging techniques. This allows for the determination of the axial length L ofthrombus14 and the axial length ofinfusion section40 oflumenal body24 offluid delivery catheter22 which will be needed to infuse thrombolytic agent A into the vicinity ofthrombus14. Once the size and location ofthrombus14 is determined,catheter10 may be deployed intoblood vessel12.

Catheter

10 is inserted intoblood vessel12 in a known manner. According to one exemplary manner, a guide wire (not shown) is advanced intoblood vessel12 to the location ofthrombus14.First catheter20 is then advanced over the guide wire to a position just proximal tothrombus14. At this point,lumenal body24 of filtering andsensing catheter22 may be moved distally forward so thatinfusion section40 is uncovered and placedadjacent thrombus14 which placesinfusion ports42 adjacent thethrombus14. The guide wire is then removed andsecond catheter70 is advanced distally throughfirst catheter20.Inner sheath100 ofsecond catheter70 is extended distally fromfluid delivery catheter22 to an extended position distal ofthrombus14 as illustrated. Thereafter, filtering andsensing catheter72 may be deployed in the manner described previously. When deployed,filtration element74 is located distal ofinfusion section40 and, when fully expanded radially, extends acrossblood vessel12. Likewise, sensingelement76 is located distal offiltration element74 and, when fully expanded radially, extends acrossblood vessel12 for thrombolytic agent sensing and embolism protection purposes.

As shown inFIG. 8, thrombolytic agent A is infused throughfluid delivery catheter22 vialumen30. The thrombolytic agent A passes throughlumen30 inannular space46 defined betweenfluid delivery catheter22 andinner sheath100. Thrombolytic agent A passes throughinfusion ports42 ininfusion section40 oflumen body24 offluid delivery catheter22 and againstthrombus14 inblood vessel12.Infusion ports42 may be nozzles to direct the thrombolytic agent A radially outward against thethrombus14. The force of the flow of thrombolytic agent A in combination with the chemically active ingredients in the thrombolytic agent A causes thethrombus14 to dissolve and dislodge, typically in pieces orfragments78, frominner surface16 ofblood vessel12.Thrombus14 breaks into fragments of dislodgedthrombotic material78 which travel withnatural fluid flow18 inblood vessel12 towardfiltration element74. Further, the thrombolytic agent A is formulated to breakdown thethrombotic material78, causing thethrombotic material78 to continue to dissolve as it flows withfluid flow18 distally towardfiltration element74.

The active thrombolytic agent A that is left in thefluid flow18 after it has passedfiltration element74 reacts withsensing element76. As described previously, the level of remaining active thrombolytic agent A downstream offiltration element74 is determined by measuring the conductivity changes C inwire mesh130. The conductivity changes C inwire mesh130 formingsensing element76 are converted to a sensing element signal that is indicative of and typically proportional to the amount of injected, active thrombolytic agent A left influid flow18 after it has passedfiltration element74. The sensing element signal is carried byfeedback component132 to the proximal end ofcatheter10 wherecontrol device134 and, optionally,display device136 are located in the illustrated embodiment. However, other transmission methods may be used to transmit the sensing element signal to the proximal end ofcatheter10 andcontrol device134 anddisplay device136 such as wireless transmission betweensensing element76 andcontrol device134 and/ordisplay device136 thereby wirelessly couplingsensing element76 andcontrol device134 and/ordisplay device136 together. Control device and/or

display device

Referring toFIGS. 10A-10B, as indicated previously, another possibility is to coat the surfaces offiltration structures120 formingfiltration element74 with an agent that is a combination of a neutralizing agent and, optionally, a material that facilitates downstream sensing of the “neutralized” thrombolytic agent A by sensingelement76. In this situation, the level of remaining active thrombolytic agent A downstream offiltration element74 is determined by measuring the conductivity changes C inwire mesh130 caused by the derived compound D which is combination of thrombolytic agent A, neutralizing or inhibiting agent, and/or an agent adapted to elicit a specific conductivity change C inwire mesh130. The conductivity changes C inwire mesh130 formingsensing element76 are converted in the same manner described previously to a sensing element signal that is now indicative of and typically proportional to the amount of neutralized thrombolytic agent A and now in the form of derived compound D left influid flow18 after it has passedfiltration element74. From the amount of neutralized or inhibited thrombolytic agent A and now in the form of derived compound D detected by sensing element, the amount of active thrombolytic agent A remaining may be determined by mathematical computation. The sensing element signal is now indicative of the amount of derived compound D detected and this is substantially the inverse of the amount of active thrombolytic agent A present downstream offiltration element74. The sensing element signal is carried byfeedback component132 to the proximal end ofcatheter10 wherecontrol device134 and, optionally,display device136 are located as described previously.

Referring toFIGS. 11A-11B, another example is to coat the surfaces offiltration structures120 formingfiltration element74 with an agent that chemically reacts with the thrombolytic agent A and neutralizes the harmful effect of the thrombolytic agent A and converts the thrombolytic agent A into a non-harmful state that may pass downstream without being chemically trapped or bound in thefiltration structures120. In this situation, the derived compound D is harmless or inert and passes freely throughwire mesh130. However, it will be clear that anythrombotic material78 which passes throughfiltration element74 is still caught or trapped by thefiltration structures120 offiltration element74. Optionally, the derived compound D may be adapted to elicit minimal or no conductivity change C inwire mesh130 ofsensing element76. However, active thrombolytic agent A is likely still present and may be sensed in the manner described previously in connection withFIGS. 9A-9B. The sensing element signal is now again indicative of the amount of active thrombolytic agent A remaining and the sensing element signal is carried byfeedback component132 to the proximal end ofcatheter10 wherecontrol device134 and, optionally,display device136 are located as described previously.

After most, if not all, of thethrombus14 is dislodged from theinner surface16 ofblood vessel12, the flow of thrombolytic agent A throughfluid delivery catheter22 is terminated. Desirably, the flow of thrombolytic agent A during the infusion process breaks down most, if not all, the fragments ofthrombotic material78 trapped in thefiltration elements120 and only a sparse few elements ofthrombotic material78 are trapped bywire mesh130 ofsensing element76. Having completed the thrombolysis,catheter10 is then removed fromblood vessel12 by, for example, reversing the steps used to deploy thecatheter10. In particular, filter andsensing catheter72 may be moved proximally, causing thefiltration structures120 offiltration element74 to collapse toward theouter surface84 oflumenal body80 and substantially parallel to the central longitudinal axis CL ofcatheter10. Any fragments ofthrombotic material78 caught infiltration elements120 will remain trapped in the collapsed configuration offiltration element74. Next, thewire mesh130 ofsensing element76 is collapsed back toward theouter surface84 oflumenal body80 of filtering andsensing catheter72. Filtering andsensing catheter72 may then be withdrawn intoinner sheath100 completing the reconstitution of second orinner catheter70.Second catheter70 is then retracted throughfirst catheter20 and removed fromblood vessel12.Fluid delivery catheter22 may be retracted intoouter sheath50 in an analogous manner as the foregoing to complete reconstitution of first orouter catheter20 and thefirst catheter20 may be removed fromblood vessel12 completing the withdrawal ofcatheter10 from blood vessel.

Referring toFIG. 13, another embodiment ofcatheter10ais shown. InFIG. 13,filtration element74 is omitted and, substantially in its place, filtering and sensing catheter72acomprises asecond infusion section160 which operates substantially as the filtration element in this embodiment.Second infusion section160 includes a plurality of distal infusion ports162 for delivering an infusate, such as a known thrombolytic agent inhibitor (a reaction agent) for neutralizing or inhibiting the active thrombolytic agent A introduced viainfusion section40aandinfusion ports42ain lumenal body24aof fluid delivery catheter22a. In effect,catheter10aoperates in a manner analogous tocatheter10 discussed in connection withFIGS. 11A-11B, whereinfiltration structures120 infiltration element74 are coated with a solid or liquid coating adapted to neutralize or inhibit the harmful effects of the injected thrombolytic agent A. In the present embodiment, the neutralizing/inhibiting agent is injected downstream and vialumenal body80aof filtering and sensing catheter72aand operates to neutralize or inhibit the thrombolytic agent A at substantially the same location where, previously,filtration element74 was located. However, it will be clear that, if desired, additional thrombolytic agent A may also be infused intoblood vessel12 vialumenal body80athroughinfusion section160 and distal infusion ports162 to treat, for example, a secondary thrombus (not shown) located distal fromthrombus14 and proximal ofsensing element76a. Additionally, a different type of therapeutic/thrombolytic agent may be infused throughinfusion section160, if desired, to treat another condition or abnormality located downstream or distal ofthrombus14.

As withinfusion section40a, distal infusion ports162 extend from an inner surface104athrough to theouter surface106aoflumenal body80aand are spaced axially apart on thelumenal body80aof filtering and sensing catheter72a. In accordance with the illustrated embodiment, distal infusion ports162 extend alonglumenal body80aof filtering and sensing catheter72ain a helical pattern, but could alternatively extend in another suitable pattern as detailed previously in connection with “upstream”infusion section40a. Distal infusion ports162 may vary in size and increase in diameter towarddistal end88aoflumenal body80aof filtering and sensing catheter72a, although it should be understood that the sizes of the infusion ports162 could be changed to another suitable configuration. Distal infusion ports162 are able to deliver infusate at a flow rate sufficient to neutralize or inhibit substantially all of the thrombolytic agent A delivered into blood vessel12aviainfusion section40aon lumenal body24aof fluid delivery catheter22a. It will be appreciated that feedback component orelement132ais desirably an insulated wire so thatfeedback component132ais shielded from conductivity effects of the neutralizing/inhibiting agent or, alternatively, a wireless connection may be used betweensensing element76aandcontrol device134 and/ordisplay device136, each shown inFIG. 1. Neutralizing/inhibiting agent is introduced into second lumen86adefined bylumenal body80aof filtering and sensing catheter72avia a suitable delivery port (not shown) incorporated as part of the proximal end90a(FIG. 7) oflumenal body80a.

Thrombolysis is performed withcatheter10ausing the same general process as described previously with regard to thecatheter10. Once first and

second catheters

20a,70aare positioned as described previously, thrombolytic agent A is infused through fluid delivery catheter22avia lumen30a. The thrombolytic agent A passes through lumen30ain annular space46adefined between fluid delivery catheter22aand inner sheath100a. Thrombolytic agent A passes throughinfusion ports42aininfusion section40aof lumen body24aof fluid delivery catheter22aand against thrombus14ain blood vessel12a.

Meanwhile and at about the same time neutralizing/inhibiting agent is directed through distal infusion ports162 fromsecond infusion section160 on thelumenal body80aof filtering and sensing catheter72a. The infused neutralizing/inhibiting agent counteracts and renders substantially inert the effects of the infused thrombolytic agent A by chemically reacting with the thrombolytic agent A thereby neutralizing the harmful effects of the thrombolytic agent A. As shown inFIG. 13, a combined/derived compound D is formed by the chemical reaction between thrombolytic agent A and neutralizing/inhibiting agent which is carried, harmless, by fluid flow18ainblood vessel12 in the direction of sensing element74a. Neutralizing/inhibiting agent converts the thrombolytic agent A into a non-harmful state “D” that may pass freely throughwire mesh130aofsensing element76a. However, it will be clear that any released and undissolved thrombotic material78aremaining in fluid flow18ais still caught or trapped by thewire mesh130aofsensing element76ain the manner described previously. Additionally, to the degree that active thrombolytic agent A is still present downstream ofsecond infusion section160, this remaining active thrombolytic material may be sensed in the manner described previously in connection withFIGS. 9A-9B.

FIG. 14 illustrates another embodiment ofcatheter10bwhich is substantially similar tocatheter10 discussed in connection withFIGS. 1-6 with certain changes to filtering andsensing catheter72bto illustrate alternative sensing arrangements for sensing the amount of active thrombolytic agent A in remaining in blood vessel12bdownstream offiltration element74b. Incatheter10b, sensing element76bextending fromlumenal body80bof filtering andsensing catheter72b, which previously in the form of aconductive wire mesh130, is replaced by a pair of light-sensingfiber optic lines164,166.Fiber optic lines164,166 are disposed withininner sheath100 and are deployable relative toinner sheath100 in generally the same manner as filtering andsensing catheter72b. In one embodiment,fiber optic lines164,166 may be secured in some manner, such as by adhesive, to the outer surface84boflumenal body80bof filtering andsensing catheter72bsuch that they are deployed simultaneously with filtering andsensing catheter72b. In such a deployed state,fiber optic lines164,166 are disposed in the vicinity offiltration element74bandfiltration structures120bin particular to monitor thefiltration element74band the amount of thrombolytic agent A present downstream or passingfiltration structures120b. As shown inFIG. 14, a distal end of eachfiber optic line164,166 is orientated and desirably biased in the direction towardfiltration structures120bto monitor the area downstream offiltration structures120band the thrombolytic agent A passingfiltration element74b. Accordingly, sensing element76b, in the present embodiment, is adapted to sense the amount of active thrombolytic agent A present (or neutralized) in blood vessel12bdownstream offiltration element74bvia reflectance principles (i.e., fluoroscopy or spectroscopy). As an example, as chemical filtration occurs infiltration element74bin the manner described previously, the chemical reaction in which thrombolytic agent A is neutralized or inhibited will provide a definitive change in light reflectance which may be monitored byfiber optic lines164,166. From the resulting change in reflectance, the amount of thrombolytic agent A neutralized/inhibited may be determined. From this determination, a mathematical computation provides the amount of active thrombolytic agent A remaining in blood vessel12bdownstream offiltration element74b.

Additionally, as illustrated a filter basket168 is provided downstream offiltration element74bin the general area previously occupied by sensingelement76 discussed previously. Filter basket168 guards against fragments of thrombotic material78btraveling unchecked through blood vessel12bdownstream fromfiltration element74b. A suitable filter basket for used as filter basked168 is disclosed in U.S. Pat. No. 6,755,813 to Ouriel et al. which is incorporated by reference herein in its entirety. It is within the scope of this embodiment to include the “sensing” function described previously in connection withsensing element76 within the wire mesh framework of filter basket168 or even to disposesensing element76 within the body of filter basket168 as an alternative. Other than the addition of filter basket168 and the use offiber optic lines164,166 in place of sensingelement76, all other aspects ofcatheter10bare consistent withcatheter10 discussed in connection withFIGS. 1-6.

As described previously,catheter10 and its use are not limited to the delivery of thrombolytic agent A toblood vessel12 described hereinabove.Catheter10 may have other applications one example of which is for the delivery of chemotherapeutic agent (doxorubicin) A to the location of malignant cancer tumors in a body lumen, cavity, and the like. Chemotherapy agents A have been used successfully in many cases to treat malignant tumors but current delivery techniques have several limitations. Additionally, these agents themselves do not affect tumor cell growth selectively, leading to high toxicity and undesirable side effects. For examples, doxorubicin is a widely used anti-cancer agent. Doxorubicin is used to treat breast cancer ovarian cancer, transitional cell bladder cancer, bronchogenic lung cancer, thyroid cancer, gastric cancer, soft tissue and osteogenic sarcomas, neuroblastoma, Wilms' tumor, malignant lymphoma (Hodgkin's and non-Hodgkin's), acute myeloblastic leukemia, acute lymphoblastic leukemia, Kaposi's sarcoma related to acquired immunodeficiency syndrome (AIDS), among others. Some common commercial names for doxorubicin are Doxil, Rubex, and Adriamycin. Doxil is doxorubicin HCL encapsulated in long-circulating (stealth) liposomes. These liposomes are formulated with surface-bound methoxypolyethylene glycol (MPEG), a process referred to as PEGylation.

Doxorubicin has a strong anti-proliferative effect over a large panel of solid tumors. Doxorubicin intercalates into DNA and breaks the strands of double helix by inhibiting topoisomerase II. Despite its clinical efficacy, Doxorubicin is not tumor selective and therefore affects healthy tissue. In so doing, doxorubicin causes severe side effects. Currently, Doxorubicin is administered intravenously as an infusion over some period of time (dependent upon concentration and other factors). As such, there is a systemic application of the drug and high cellular collateral damage. Toxic side effects of systemically delivered doxorubicin include nausea and vomiting which may last up to 24-48 hours after treatment, loss of appetite, diarrhea, difficulty swallowing, thinned or brittle hair, skin irritation (sunburn-like) or rash on areas previously exposed to radiation treatments, darkening of fingernails or toenails, swelling, pain, redness, or peeling of skin on the palms and soles of the feet.

Referring toFIGS. 1-6 again,catheter10 would operate in much the same manner with doxorubicin as the chemotherapy agent A as described previously with the administered therapeutic agent being thrombolytic agent A such as tPA. In this specific use case,catheter10 is inserted into a patient's vascular system, generally through the femoral artery.Catheter10 is maneuvered through the vascular system until it is positioned in proximity to the tumor or cancerous tissue. Chemotherapy agent A is infused throughfluid delivery catheter22 vialumen30. The chemotherapy agent A passes throughlumen30 inannular space46 defined betweenfluid delivery catheter22 andinner sheath100. Chemotherapy agent A passes throughinfusion ports42 ininfusion section40 oflumen body24 offluid delivery catheter22 and against the tumor (not shown) which will be located in the location ofthrombus14 inFIGS. 2-4.Infusion ports42 may be nozzles to direct the chemotherapy agent A radially outward against the tumor. The chemotherapy agent A then travels influid flow18 past the target area of cancerous tissue to some point distal, tofiltration element74.

catheter

10a,10bshown inFIGS. 12-13 and14 respectively may be used to treat and neutralize chemotherapy agent A in the manner described previously in this disclosure.

Due to the ability to neutralize doxorubicin, more concentrated doxorubicin can be released without fear of causing systemic toxic reactions. Toxic reactions will be limited to that area betweeninfusion section40 oflumenal body24 offluid delivery catheter22 andfiltration element74. This has the potential of decreasing the number of chemotherapy sessions that a patient must endure.

While several embodiments of a therapeutic agent delivery apparatus and methods associated therewith were described in the foregoing detailed description, those skilled in the art may make modifications and alterations to these embodiments without departing from the scope and spirit of the invention. Accordingly, the foregoing description is intended to be illustrative rather than restrictive. The invention described hereinabove is defined by the appended claims and all changes to the invention that fall within the meaning and the range of equivalency of the claims are embraced within their scope.

Claims

1. A method of infusing a therapeutic agent into a body lumen, comprising:

inserting a lumenal body into the body lumen, the lumenal body defining at least one infusion port for infusing the therapeutic agent into the body lumen;

infusing the therapeutic agent into the body lumen; and

sensing the amount of infused therapeutic agent or any compound derived from the therapeutic agent in the body lumen with a sensing element disposed distal of the at least one infusion port.

2. A method as claimed inclaim 1, comprising providing a sensing element signal to a location outside the body lumen with a feedback component associated with the sensing element.

3. A method as claimed inclaim 2, wherein the sensing element signal is provided to a user interface.

4. A method as claimed inclaim 2, wherein the sensing element signal is represented to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of the audible, visual, and tactile stimuli.

5. A method as claimed inclaim 2, wherein the sensing element signal is proportional to the amount of therapeutic agent or derivative thereof sensed by the sensing element.

6. A method as claimed inclaim 1, wherein the sensing element senses the amount of therapeutic agent or derivative thereof by one or more of resonant detection, light reflectance, and electrical conductivity changes.

7. A method as claimed inclaim 1, comprising intercepting at least some of the therapeutic agent or derivative thereof in the body lumen with the sensing element.

8. A method as claimed inclaim 1, comprising infusing additional therapeutic agent, a different therapeutic agent, or a reaction agent adapted to react with the therapeutic agents into the body lumen through at least one distal infusion port proximal of the sensing element.

9. A method as claimed inclaim 1, comprising filtering the therapeutic agent or derivative thereof in the body lumen with a filtration element disposed distal of the infusion ports and proximal of the sensing element.

10. A method of infusing a therapeutic agent into a body lumen, comprising:

infusing the therapeutic agent into the body lumen; and

delivering a reaction agent adapted to react with the therapeutic agent in the body lumen with a filtration element disposed distal of the at least one infusion port.

11. A method as claimed inclaim 10, wherein the reaction agent is coated on the filtration element and filtering of the therapeutic agent occurs by contact between the coated filtration element and the therapeutic agent.

12. A method as claimed inclaim 10, wherein in the reaction agent is delivered by infusing the reaction agent through at least one distal infusion port forming the filtration element.

13. A method as claimed inclaim 12, comprising sensing the amount of infused therapeutic agent or any compound derived from the therapeutic agent in response to the reaction agent in the body lumen with a sensing element disposed distal of the at least one distal infusion port.

14. A method as claimed inclaim 10, comprising sensing the amount of infused therapeutic agent or any compound derived from the therapeutic agent in response to the reaction agent in the body lumen with a sensing element disposed distal of the filtration element.

15. A method as claimed inclaim 14, comprising providing a sensing element signal to a location outside the body lumen with a feedback component associated with the sensing element.

16. A method as claimed inclaim 15, wherein the sensing element signal is provided to a user interface.

17. A method as claimed inclaim 15, wherein the sensing element signal is represented to a user as an audible, visual, or tactile stimulus or a combination stimulus comprising one or more of the audible, visual, and tactile stimuli.

18. A method as claimed inclaim 15, wherein the sensing element signal is proportional to the amount of therapeutic agent or derivative thereof sensed by the sensing element.

19. A method as claimed inclaim 14, wherein the sensing element senses the amount of therapeutic agent or derivative thereof by one or more of resonant detection, light reflectance, and electrical conductivity changes.

20. A method as claimed inclaim 14, comprising intercepting at least some of the therapeutic agent or derivative thereof in the body lumen with the sensing element.