In vivo localization and tracking of tissue penetrating catheters using magnetic resonance imaging

[0001] This patent application is a continuation-in-part of copending U.S. patent application Ser. No. 10/467,274 entitled “Methods and Apparatus for Guided Transluminal Interventions Using Vessel Wall Penetrating Catheters and Other Apparatus” filed Aug. 5, 2003, which is national stage application of PCT/US02/03941 filed on Feb. 2, 2002, which claims priority to U.S. Provisional patent Application No. 60/266,800 filed on Feb. 6, 2001, the entire disclosure of each such related application being expressly incorporated herein by reference.

[0002] The present invention relates generally to methods and apparatus for medical treatment and more particularly to magnetic resonance image (MRI) guided tissue penetrating catheters and their methods of use.

[0003] High resolution MRI techniques have proven to be useable for assessing the anatomy of various blood vessels, including coronary blood vessels, as well as pathological lesions on blood vessel walls. see, Shinnar, M. et al., The Diagnostic Accuracy of Ex Vivo MRI for Human Atherosclerotic Plaque Characterization; Arterioscler. Thromb. Vasc. Biol. 19:2756-2761 (1999) and Hatsukami, T. S., et al., Visualization of Fibrous Cap Thickness and Rupture in Human Atherosclerotic Carotid Plaque In Vivo With High-Resolution Magnetic Resonance Imaging. Circulation 102:959-964 (2000). Also, because MRI is sensitive to changes in temperature, it can be used to assess temperature differences within the body or to monitor heat-based therapies.

[0004] The advent of rapid image acquisition sequences has rendered MRI useable as a means for guiding the in vivo positioning of guidewires, catheters and other interventional devices. For example, researchers have devised MRI guidable catheters and guidewires that incorporate MRI antennae and real-time visualization of a guidewire, guiding catheter, and anatomy has been accomplished. See, Serfaty, Jean-Michael, et al., Toward MRI-Guided Coronary Cathetrization: Visualization of Guiding Catheters, Guidewires and Anatomy in Real Time, J. Mag. Reson. Imaging, 12:590-594 (2003). Examples of MRI apparatus (e.g., coils) that may be mounted on or in catheters or other instruments and associated methods to facilitate MRI guidance of such catheters and instruments are described in U.S. Pat. Nos. 5,217,400 (Dumoulin et al.), 5,307,808 (Dumoulin et al.), 6,393,314 (Watkins et al.), 6,332,088 (Zhang et al.), 6,198,962 (Su), 6,198,962 (Su) and 6,171,240 (Young), the entire disclosure of each such United States patent being expressly incorporated herein by reference. One example of a side exit catheter operated using MRI guidance includes United States Patent Application Publication US 2003/32936 (Lederman) entire disclosure expressly incorporated herein by reference. To date, MRI guidance has not yet been used for guidance of tissue penetrating catheters from blood vessels.

[0005] In general, tissue penetrating catheters are inserted into blood vessels or other natural or man-made body lumens and advanced to a desired position. A tissue penetrator is then advanced from the catheter to a target location outside of the body lumen in which the catheter is positioned. A substance (e.g., a drug, biologic, cells, filler or other material), device (e.g., a guidewire, catheter, electrode, light guide, substance delivery implant, tool, scope, etc.) or other therapy (e.g., laser, ionizing radiation, etc.) may then be delivered by or through the tissue penetrator to the target location. In some instances the target location may be within the wall of the blood vessel or other luminal anatomical structure in which the catheter is positioned. In other instances, the target location may be another anatomical or pathological structure (e.g., a blood vessel, organ, body cavity, tumor, muscle, nerve, etc.). Examples of tissue penetrating catheter systems and their methods of use include those described in U.S. Pat. Nos. 5,830,222 (Makower), 6,068,638 (Makower), 6,159,225 (Makower), 6,190,353 (Makower, et al.), 6,283,951 (Flaherty, et al.), 6,375,615 (Flaherty, et al.), 6,508,824 (Flaherty, et al.), 6,544,230 (Flaherty, et al.), 6,579,311 (Makower), 6,602,241 (Makower, et al.), 6,655,386 (Makower, et al.), 6,660,024 (Flaherty, et al.), 6,685,648 (Flaherty, et al.), 6,709,444 (Makower), 6,726,677 (Flaherty, et al.) and 6,746,464 (Makower) the entire disclosure of each such United States patent being expressly incorporated herein by referenceImage guidance of tissue penetrating catheters can present unique challenges not associated with other types of catheters. For example, it is sometimes desirable for the operator to be provided with, not only an indication of the catheter's position within the body, but also an indication of the catheter's rotational orientation relative to the target location and/or other indication of the trajectory on which the penetrator will advance. Such indication of catheter rotational orientation and/or penetrator trajectory enables the operator to pre-orient the catheter so that, when the tissue penetrator is subsequently advanced, it will enter the target location and not some other unintended location. Thus, there remains a need in the art for the development of MRI guidable tissue penetrating catheters and related methods of use.

[0006] In accordance with the present invention there is provided a tissue penetrating catheter device that is useable in conjunction with an available MRI system such as from GE Medical Systems, Waukesha, Wis.; Siemens Medical Solutions of Siemens AG, Malvern, Pa. and Erlangen, Germany; Toshiba America Medical Systems, Inc., Tustin, Calif. as well as any other suitable MRI system. Such tissue penetrating catheter device comprises a catheter body, a tissue penetrator that is advanceable from the catheter body and at least one magnetic resonance apparatus that sends signals to the magnetic resonance imaging system. The magnetic resonance imaging system is adapted to use such signals to provide an indication of the position of the magnetic resonance apparatus and, thus, the in vivo position of the catheter body. The magnetic resonance apparatus located on or in the catheter body may comprise a magnetic resonance receiver, such as a coil or antenna (e.g., a loopless antenna). In some embodiments, the catheter device may include a magnetic resonance apparatus that indicates the path on which the penetrator will subsequently advance from the catheter body and/or the rotational orientation of the catheter body within the subject's body and/or the radial location of an opening or other discrete radial location on the catheter from which the penetrator will advance, relative to the target location. Such indicia of penetrator path, rotational orientation or radial penetrator outlet location may be used by the operator to adjust the rotational orientation of the catheter body prior to advancement of the penetrator to ensure, or at least increase the likelihood, that the penetrator will advance to the target location rather than some other location. In some embodiments, the tissue penetrator may be an elongate penetrator member (e.g., a needle) having a hollow lumen through which a substance, article or device may be introduced.

[0007] Further in accordance with the invention, there are provided methods for creating a penetration tract from a location within a body lumen (e.g., a blood vessel lumen or other natural or man-made anatomical passageway) to a location outside of that body lumen. Such method generally comprises the steps of (A) providing a tissue penetrating catheter device that comprises i) a catheter body having a distal end, ii) a tissue penetrator that is advanceable from the catheter body and iii) at least one magnetic resonance apparatus that sends signals to a magnetic resonance imaging system adapted to use said signals to provide an indication of the current position of said at least one magnetic resonance apparatus; (B) inserting the tissue penetrating catheter into the subject's body; (C) causing a magnetic resonance imaging system to receive signals from said at least one magnetic resonance apparatus and to provide, in response to the received signals, an indication of the current position of the at least one magnetic resonance apparatus within the subject's body; (D) using the indication of the current position of the at least one magnetic resonance apparatus within the subject's body to guide the tissue penetrating catheter to a position within said body lumen near the target location, and (E) advancing the tissue penetrator from the tissue penetrating catheter to the target location. In some embodiments, the tissue penetrating catheter device will include a magnetic resonance apparatus that provides indicia of the path on which the penetrator will subsequently advance from the catheter body and/or the rotational orientation of the catheter body within the subject's body and/or the radial location of an opening or other discrete radial location on the catheter from which the penetrator will advance, relative to the target location, and the operator may use such indicia to adjust the rotational orientation of the catheter within the subject's body as necessary to ensure, or at least increase the likelihood, that the penetrator will advance in Step E to the intended target location rather than some other location. In some embodiments, the tissue penetrator may be an elongate penetrator member (e.g., a needle) having a hollow lumen through which a substance, article or device may be introduced and the method may further include the step of introducing a substance (e.g., a therapeutic or diagnostic substance), article (e.g., an implant) or device (e.g., a guidewire, catheter, apparatus, etc.) through the penetrator lumen.

[0008] Further aspects, details and embodiments of the present invention will be understood by those of skill in the art upon reading the following detailed description of the invention and the accompanying drawings.

[0015] The Figures are not necessarily to scale.

[0016] The following detailed description, the accompanying drawings are intended to describe some, but not necessarily all, examples or embodiments of the invention. The contents of this detailed description and accompanying drawings do not limit the scope of the invention in any way.

[0017] FIGS. 1-1D show one of many possible examples of an MRI guidable tissue penetrating catheter device 10 of the present invention. This catheter device 10 is useable in conjunction with a separate MRI system 26 that is programmed to receive and process signals from MRI apparatus 34, 35, 46 mounted at different positions on the catheter device 10. In the preferred embodiment shown, each MRI apparatus 34, 35, 46 comprises a coil. Each coil may be made of a conductive material and is shielded along the majority of its length to inhibit interference as is well known in the art. Although in the preferred embodiment coils are provided, it should be understood that other devices to create an image in an MRI image may also be used. Although an object which is literally a coil is used in the preferred embodiment, the invention may be practiced using any other suitable receiving structure, including objects which may not be literally a coil. Also, it should be noted that the coil does not need to be coaxial with the member it is intended to track. It can be a planar coil that is adjacent to or touching or embedded within the member being tracked. Each coil is connected to the proximal end of the catheter device 10 to a proximal connector 24a, 24b and/or 24c. Each proximal connector is, in turn, connected to the MRI system 26 through an impedance matching circuit as is well known in the art such that signals from the MRI apparatus 34, 35, and/or 46 (e.g., the coils) are received by the MRI system 26. The MRI system 26 is programmed to display, in response to such signals received from MRI apparatus 34, 35, and/or 46, the positions of such MRI apparatus 34, 35, and/or 46 relative to anatomical structures within the subject's body in a so-called real time manner. In an alternative embodiment, the MRI apparatus may be superimposed into a prior MRI imaging scan stored in memory using known techniques. In a further embodiment immobile landmarks (such as a bony prominences) may be used as internal fiducials to superimpose historical with current or real-time images for such tracking. This may be accomplished using image-rendering software employing known techniques.

[0018] In general, this example of the catheter device 10 comprises an elongate, flexible catheter body 12 and a handpiece 14. A side port 41 is formed in the sidewall of the catheter body, as seen in FIG. 1A. A tissue penetrator 30 is moveable between a retracted position, where at least the distal portion of the penetrator 30 is within a curved tubular penetrator housing 40 as seen in FIG. 1C, and an extended position wherein the penetrator 30 extends out of side port 41, as shown in FIG. 1A.

[0019] It will be appreciated that the penetrator 30 may comprise any member (e.g., a probe or needle), apparatus (e.g., an electrosurgical probe) or energy form (e.g., laser beam) capable of penetrating tissue. In the particular embodiment shown in the drawings, the penetrator 30 comprises a curved needle having a hollow lumen 32 and an open distal end. A proximal side arm 27 is connected to the proximal end of the penetrator lumen 32 such that a substance, article or device may be delivered through the proximal side arm 23 and through the lumen 32 of the penetration member 30. In the particular example shown in FIGS. 1 and 1A, a non-ferrous guidewire 23 (e.g., a 0.014-inch nickel titanium alloy guidewire available Terumo Medical Corporation, Somerset, N.J.) is advanced through proximal side arm, 27, through the lumen 32 of the penetrator 30 and out of the distal end of the penetrator 30. Some non-limiting examples of other devices, articles and substances that may be delivered through the penetrator lumen 32 are described below.

[0020] With reference to FIG. 1, the handpiece 14 comprises a penetrator advancement/retraction knob 15 which may be pushed in the distal direction to advance the penetrator 30 from its retracted position to its extended position and pulled in the proximal direction to retract the penetrator from its extended position to its retracted position. An adjustable stop member 17 limits the extent of distal advancement of the penetrator advancement/retraction knob 15, thereby controlling the length from the side port 28 to the distal tip of the penetrator 30 when the penetrator 30 is fully extended.

[0021] A tube 36 extends from a proximal port 16 on the handpiece 14 through the catheter body. A tapered distal tip member 39 having a lumen 38 is mounted on the distal end of the catheter body 12. The distal tip member lumen 38 is continuous with the lumen 38 of tube 36, such that a continuous lumen extends from proximal port 16 though the open distal end of distal tip member 39. A guidewire 25 may pass through this lumen 38, 38 (tip) for over-the-wire advancement of the catheter device 10. It will be appreciated that, in some alternative embodiments, the lumen 38 may terminate proximally in a side opening in the catheter body 12, thereby providing a rapid exchange type guidewire lumen.

[0022] In the embodiment shown in FIGS. 1-1D, an infusion port 18 is optionally formed on the handpiece 14 in communication with lumen 38 such that an infusion apparatus 20 (e.g., a syringe, intravenous tube, pump, injector, etc.) may be used to infuse fluid (e.g., saline solution, radiographic contrast medium, etc.) through lumen 38, 38 (tip) and out of the open distal end of the tip member 46. A valve (e.g., a Tuoghy Borst valve) may be provided on proximal port 16 to secure a guidewire 25 when desired and/or to form a fluid tight seat at proximal port 16 when fluid is being infused through infusion port 18.

[0023] The catheter device 10 shown in this example incorporates three (3) MRI apparatus 34, 35, 46 (e.g., the coils), each of which indicates the in vivo position and/or rotational orientation of a different portion of the catheter device 10.

[0024] A first MRI apparatus 34 comprises an MRI receiver coil wound about the penetrator 30 at a location near its distal end, such that first MRI apparatus 34 will indicate the position of the distal portion of the penetrator 30 on the MRI system display. This enables the operator to determine, from an MRI display, when the distal end of the penetrator has entered an intended target location.

[0025] Second MRI apparatus 35 comprises an MRI receiving coil wound about the curved needle housing 40, such that second MRI apparatus 35 will indicate on the MRI display the location of the needle housing 40. Additionally, by providing an image of the curvature of the needle housing, second MRI apparatus 35 will indicate the rotational orientation of the catheter body 12 and, thus, the path or trajectory on which the penetrator 30 will subsequently advance.

[0026] Third MRI apparatus 46 comprises an MRI receiving coil wound about the distal tip member 39, near the distal end DE of the catheter body. This enables the operator to determine, from an MRI display, the real time in vivo location of the distal end DE of the catheter device 10.

[0027] FIGS. 2A-2C show an example of a method by which the catheter device 10 may be used. Each of FIGS. 2A-2C shows a diagram of the catheter body 12 positioned within a body lumen BL (e.g., a blood vessel) on the left and a corresponding MRI system display on the right.

[0028] In FIG. 2A, the catheter body 12 is positioned within the body lumen BL and rotationally orientated such that the side opening 41 from which the penetrator 30 will emerge is rotated approximately 90 degrees away from the target location TL. Accordingly, the MRI system display in FIG. 2A shows the second MRI apparatus image 35i as a straight line adjacent to the target location TL and aligned directly behind the third MRI apparatus image 46i indicating the position of the distal end of the catheter body 12 within the body lumen BL. From this image, the operator can see that the longitudinal position of the catheter body 12 is generally suitable but the rotational orientation of the catheter body is off by approximately 90 degrees. Thus, if the penetrator 30 were to be advanced while the catheter body 12 is in its current rotational orientation, the penetrator 30 would not enter the target location TL but rather would penetrate into other tissue adjacent to the body lumen BL, potentially causing unwanted trauma or damage.

[0029] In FIG. 2B, the operator rotates the catheter body 12 until the third MRI apparatus image 46i on the MRI system display shows the curvature of the penetrator housing 40 pointing directly toward the target location TL. This indicates to the operator that the catheter body 12 is properly positioned and oriented for subsequent advancement of the penetrator 30 to the target location TL.

[0030] In FIG. 2C the penetrator 30 is advanced out of opening 41, through the wall of the body lumen BL in which the catheter body 12 is positioned and into the target location TL. The first MRI apparatus image 34i shown on the MRI system display indicates to the operator that the distal end of the penetrator 30 has entered the target location, as desired. At this time, any desired device, article or substance may be delivered though the penetrator lumen 32 to the target location TL.

[0031] It should be noted that different MRI apparatus 34, 35, 46 (e.g., the coils) can be linked to different channels in the MRI system, such that each coil (and thus the device region it is tracking) can be depicted on the MRI image in a different color. Such an embodiment may permit navigation more user-friendly.

[0032] One particular advantage of the present invention is that it may allow the use of an MRI for delivery materials to areas requiring the discrimination of an MRI to identify (e.g. infarcted or ischemic tissue, tumor, etc.). In FIG. 2A-c such a region was depicted as target location TL. Because an MRI illustrates and displays well areas of infarction or ischemia, the present invention is believed to be particularly useful to visualize and locate exactly where an area of infarction or ischemia is and thus better able to deliver drugs, etc right into such an area. Moreover, while this benefit is depicted as permitting discerning non-viable from viable myocardium, it may also be used to advantage for delivering a therapy-containing catheter to any other type of damaged or non-viable tissue (nerve, muscle, liver, spleen, pancreas, kidney, brain, etc.).

[0033] It is to be appreciated that the catheter device 10 and method may be used for many different purposes wherein it is desired to penetrate from a location within a body lumen to some target location outside of that body lumen. In some instances, the target location may be in the wall of a vessel in which the catheter body 12 is positioned. For example, the wall of a blood vessel is made up of several layers (e.g., tunica intima, tunica media and tunica adventitia or outer coat) and the penetrator 30 may be advanced from the lumen of the blood vessel to a location within the blood vessel wall (e.g., into the adventitia or outer coat of the blood vessel. This technique may facilitate delivery of therapeutic substances into the luminal vessel wall. For example, this technique may be used for injection of drugs into an artery wall to deter restenosis of the artery following an angioplasty procedure.

[0034] In other instances, the target location may be outside of the wall of the luminal anatomical structure in which the catheter body 12 is positioned and the penetrator 30 may be advanced all the way through the luminal wall to the desired target location. For example, the catheter body 12 may be positioned within the lumen of one blood vessel and the penetrator 30 may be advanced to a target location within the lumen of another blood vessel. Such vessel-to-vessel penetration may be utilized to create, or to facilitate the creation of, a passageway or fistula between two blood vessels. Or, as a further example, the target location may be a natural or man made cavity or structure located adjacent to or a spaced distance away from the body lumen in which the catheter body 12 is positioned. Examples of such possible target locations include organs, tumors, body cavities, previously implanted devices such as substance reservoirs or drug eluting devices, etc. Targets may also include different layers within an organ or tissue such as the potential space between two tissue layers. For example, the target may be the sub-endocardium or the sub-epicardium.

[0035] Also, in some instances, the penetration catheter 10 may be inserted into a man made passage such as a guidewire tract or neo-lumen created in the wall of a blood vessel past an occlusive lesion (e.g., a chronic total occlusion) and the penetrator 30 may then be advanced to a target location within the true lumen of that blood vessel downstream of the obstruction. In such procedures, if the penetrator 30 has a lumen 32, a guidewire may be advanced through the penetrator lumen 32 into the true lumen of the blood vessel downstream of the obstruction. Thereafter, the penetrator 30 may be retracted and the penetrating catheter device 10 removed, leaving the guidewire in place. A stent may then be delivered over that guidewire and used to stent the man made guidewire tract (e.g., “neo-lumen) thereby providing a bypass conduit for blood flow around the obstructive lesion.

[0036] In applications of the invention where a flowable substance is to be delivered via the penetrator 30 to the target location, it will be appreciated that the substance may in some cases be delivered directly though a lumen 32 formed in the penetrator 30 and in other cases a separate catheter may be advanced through the lumen 32 of the penetrator 30 and the flowable substance may then be delivered through that separate catheter. Examples of the types of substances that may be delivered include but are not limited to: contrast agents or other agents that provide an enhanced image of the target site, traceable substances that may be used to determine the rate at which the substance distributes away from or is otherwise inactivated at the target site or other pharmacokinetic or biodistributive parameters or variables, drugs, proteins, cells (e.g., stem cells, nerve cells, progenitor cells, myoblasts, myocytes, secretory cells, pancreatic islet cells, dopamine secreting cells, endothelial cells, hepatocytes, cloned cells, cells grown in cell culture, genetically modified cells, and combinations thereof), angiogenic substances (e.g., vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF) or scatter factor, heparin combined with an adenosine receptor agonist, nerve cell growth factor (NGF), and combinations thereof), other agents that increase vascularity of an ischemic target site, myogenic substances, neurogenic substances, genes, gene therapy compositions, genetic material in combination vectors (e.g., viruses), stem cells of a type that will mature in situ into a type of cell that is currently deficient, substances that promote the growth of myocytes in tissue that is necrotic or characterized by a lack of living myocytes, secretory cells that secrete a substance (e.g., dopamine, insulin, a particular neurotransmitter) that is deficient, tep F comprises insulin secreting cells, glial cell line-derived neurotropic factor (GDNF), nerve growth factor, neuro-immunophilin ligand, poly ADP-Ribose polymerase, and combinations thereof.

[0037] In applications of the invention where an article is to be delivered to the target site, it will be appreciated that in some cases such article may be introduced directly through the lumen 32 of the penetrator 30 and in other cases a tube or other delivery device may be advanced through the penetrator 30 and used to deliver the desire article. Examples of the types of articles that may be delivered include but are not limited to; substance eluting implants, radioactive implants, embolic members, markers, as well as radiopaque markers, etc.

[0038] In applications of the invention where a device is to be delivered to the target site, it will be appreciated that in some cases such device may be introduced directly through the lumen 32 of the penetrator 30 and in other cases a delivery device (e.g., a guidewire or catheter) may initially be advanced through the lumen 32 of the penetrator 30 and second device (e.g., a working device) may then be delivered to the target location by way of that delivery device. Examples of the types of articles that may be delivered include but are not limited to; catheters, cannulae, guidewires, wires, electrodes, sensors, microreservoirs, implantable devices, substance eluting or delivering devices, etc.

[0039] It is to be further appreciated that the invention has been described hereabove with reference to certain examples or embodiments of the invention but that various additions, deletions, alterations and modifications may be made to those examples and embodiments without departing from the intended spirit and scope of the invention. For example, any element or attribute of one embodiment or example may be incorporated into or used with another embodiment or example, unless to do so would render the embodiment or example unsuitable for its intended use. Also, where the steps of a method or process are described, listed or claimed in a particular order, such steps may be performed in any other order unless to do so would render the embodiment or example not novel, obvious to a person of ordinary skill in the relevant art or unsuitable for its intended use. All reasonable additions, deletions, modifications and alterations are to be considered equivalents of the described examples and embodiments and are to be included within the scope of the following claims.