Abstract:
A catheter ( 100 ) is disclosed that includes a reinforced hollow fiber ( 114 ) and is suitable for insertion- in a body tissue in order to deliver and/or recover fluids to and/or from the tissue. In one embodiment, the catheter comprises a combination of catheter body ( 112 ), hollow fiber region ( 114 ), and reinforcing means ( 116 ), to provide a catheter having sufficient structural integrity for the hollow fiber region to be positioned within a body tissue, preferably without the need for ancillary devices such as introducers or protective sheaths, and to there be used for the purpose of delivering and/or recovering fluids from the surrounding tissue.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application claims priority to International Application No. PCT/US2009/047489 filed Jun. 16, 2009, which in turn claims priority to US Provisional Application No. 61/061,895 filed Jun. 16, 2008, the teachings of which are incorporated herein by reference. 
     FIELD OF THE INVENTION 
     The invention relates to catheters used for convection enhanced delivery of therapeutic fluids to specific remote anatomical locations in a mammalian body. 
     BACKGROUND 
     Millions of Americans are afflicted by neurogenerative and malignant diseases affecting the central nervous system (CNS). For many of these diseases, such as Parkinson&#39;s, Alzheimer&#39;s and high grade primary brain tumors, there is currently no curative therapy. An extensive effort has been taken to develop and test novel drugs, cell-based therapies, and gene therapy to treat these disorders. It is clear that even when effective therapeutic agents are identified, delivery into the CNS at therapeutic concentrations and sufficient distribution is a rate-limiting step to achieving clinical efficiency. The blood-brain barrier is composed of closely adhering endothelial cells, pericytes and astrocytes that tightly regulate the diffusion of molecules into the brain parenchyma. Substances with a molecular weight higher than 500 Daltons generally cannot cross the blood-brain barrier, while smaller molecules often can. Many drugs are unable to pass the barrier since the majority of them are heavier than 500 Daltons. Although efforts focused on achieving blood-brain barrier disruption and advances in endovascular delivery have shown promise, many agents such as tumor-targeted toxins, genetic vectors and chemotherapy have undesirable pharmacologic problems and systemic side effects when administered intravenously. Overcoming the drug-delivery obstacles to the CNS is a critical step in attaining better clinical outcomes. 
     Direct infusion of drugs into the brain parenchyma using convection-enhanced delivery (CED) results in the treatment of large areas of brain tissue and concentrates the infusate in situ, thereby circumventing the delivery obstacles posed by the blood-brain barrier and dilution of infusate in the blood. CED is a technique that relies on bulk flow to establish a pressure gradient over time, resulting in continuous convective flow and widespread distribution of the infusate to the affected areas of the brain. The extent of drug distribution using CED depends on many factors including: (1) interstitial pressure; (2) type of tissue infused (tumor, grey matter, white matter); (3) molecular weight of infusate; (4) volume and flow rate during administration; and (5) diameter/type of drug delivery catheter. 
     One limitation related to conventional CED treatment involves the backflow of infusate along the catheter body at increased infusion rates, which can be exasperated following introduction using a removable introducer. Backflow generally occurs as a result of excessive fluid infusion pressure at higher flow rates that preferentially drives the fluid up the catheter shaft as the path of least resistance. When using an introducer to place the catheter in tissue and due to the outer diameter of the introducer being necessarily greater than the outer diameter of the drug delivery catheter, this creates a post-introducer tissue compression, thereby creating a preferential gap and lower flow resistance along the catheter body, resulting in increased backflow or reflux of infusate during treatment at high injection flow rates as compared to catheters placed without introducers. 
     Another limitation relates to uneven distribution of infusate in brain tumor tissue as opposed to normal brain tissue. While the interstitial pressure of normal brain tissue is relatively low, (1-2 mm Hg), the interstitial pressure in brain tumor tissue can be over twenty-five times greater, which may account for uneven distribution and leakage of infusate into the subarachnoid space. This phenomenon is not surprising considering that most catheters used for CED have a single lumen from which infusate is delivered and the infusate may follow the path of lowest interstitial pressure. Additionally, it has been documented that multiport catheters may only infuse through one or two ports (that have least resistance to outflow) when eight are present, rendering the majority of ports useless for drug delivery. As an example, gliomas are composed of necrotic areas and regions of infiltrating tumor cells into the normal brain tissue, therefore the interstitial pressure varies greatly, creating counterproductive pressure gradients in peritumoral tissue. Use of CED in normal brain tissue with low flow rates (i.e., 0.1 μl/min) results in relatively homogenous distribution, but higher flow rates (i.e., 5 μl/min) results in reflux of the infusate back along the catheter track and away from the target tissue. Attempting to infuse large volumes, over a short time period, results in a deforming force on tissue, eventually narrowing the interstitial space and promoting a shear plane and tissue tearing. Therefore, a long administration time is required to administer even 1 ml of infusate because higher flow rates negate the desired distribution of drug using CED. What is clearly needed, therefore, and would be beneficial to treating brain tumor patients by CED, are new types of catheters and methods capable of increasing flow rate and decreasing total infusion time thereby shortening clinical procedures, while also minimizing reflux and allowing for more homogenous delivery of infusate. 
     Hollow fiber membranes are made from porous polymers and have been incorporated into catheters that improve the distribution of drugs administered directly into the central nervous system and other tissues. It has been found that using a porous polymer hollow fiber significantly increases the surface area of brain tissue that the drug or therapeutic fluid is infused into. Hollow fiber membranes create a very low pressure for fluid injection such that the risk for backflow is reduced while creating overall higher flow rates with the large surface area of the hollow fiber membrane. Dye was infused into a mouse brain by convection-enhanced delivery using a 28 gauge needle compared to a hollow fiber having a 3 mm length. Hollow fiber mediated infusion increased the volume of brain tissue labeled with dye by a factor of 2.7 times compared to using a needle. In order to determine if hollow fiber use could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo luminescent imaging. In vivo imaging revealed that hollow fiber mediated infusion of adenovirus resulted in gene expression that was an order of magnitude greater than when a conventional needle was used for delivery. To assess distribution of gene transfer, an adenovirus expression green fluorescent protein was injected into the striatum using a hollow fiber and a conventional needle. The hollow fiber greatly increased the area of brain transduced with adenovirus relative to a needle, transducing a significant portion of the injected hemisphere as determined by histological analysis. 
     On a separate subject, Applicant has previously disclosed and claimed various applications for the use of hollow fibers in various medical applications, including microdialysis, ultrafiltration and so forth. See, for instance, PCT application serial numbers PCT/US98/16416, filed 7 Aug. 1998, PCT/US03/08921, filed 21 Mar. 2003 and corresponding U.S. applications, all of which are incorporated herein by reference. 
     SUMMARY 
     The present invention provides a catheter that comprises a reinforced catheter including a hollow fiber suitable for insertion in a body tissue in order to deliver and/or recover (e.g., aspirate) fluids from the tissue, and which is then subsequently suitable for safe removal from the body tissue. In a preferred embodiment, the catheter comprises a combination of catheter body, hollow fiber region, and reinforcing component(s), which can be provided in any suitable combination and arrangement, to provide a catheter having sufficient structural integrity for the hollow fiber region to be positioned within a body tissue, optionally without the need for ancillary devices such as introducers or protective sheaths, and to there be used for the purpose of delivering and/or recovering fluids from the surrounding tissue, and then to be removed from the body tissue. 
     Typically, the catheter body will include a substantially solid body portion adapted to be coupled with and extend proximally from the hollow fiber region. Included also will be one or more reinforcing components, adapted to provide the hollow fiber region with sufficient properties (e.g., strength, flexibility and patency) to permit the hollow fiber region to remain in place and be used to deliver and/or recover fluids. 
     In one preferred embodiment, a removable rigid stylet can be included as well, and used to reinforce the catheter for insertion into tissue, e.g., by positioning the stylet within the catheter. It is generally desirable to remove the rigid stylet after positioning the catheter in the targeted tissue, so as to minimize tissue trauma from inadvertent movement of the catheter with a rigid stylet. In this manner, the catheter, including the hollow fiber region, can be retained in position after positioning of the catheter into body tissue using the rigid stylet, and prior to treatment (e.g., delivery and/or removal of fluid). 
     The hollow fiber region, in turn, will be of sufficient type, size, dimensions, configuration and porosity to permit it to remain positioned within a body tissue, including during stylet removal, and there used to deliver or recover fluids (including the recovery of fluid components, e.g., liquid and small solutes). The hollow fiber region can be coupled to the reinforcing component(s) and/or to the catheter body at or near its proximal end, and extend distally therefrom. 
     More preferably, one or more reinforcing components can be used to support the hollow fiber while in position and use within the body. Such reinforcing components can be provided in any particular form, e.g., in the form of one or more relatively flexible rods or tubes, which can be positioned in a suitable manner with respect to the catheter body and hollow fiber region, to permit the overall catheter, and particularly the distal hollow fiber region, to be used within and removed from tissue. 
     Reinforcing components can be provided by the use of materials having sufficient properties (e.g., rigidity, flexibility, strength, dimensions) to permit them to be positioned and used with respect to both the catheter body and hollow fiber region. Reinforcing components can be formed, for instance, of suitably flexible materials, including synthetic or nature materials such as metals, polymeric materials, and combinations thereof. A reinforcing component (e.g., flexible material) can be fabricated and used in any suitable shape, e.g., a solid rod or tubular, and can be positioned in any suitable manner with respect to both the catheter body and hollow fiber region, e.g., one or more rods or tubes can be positioned internally and/or externally to the catheter body and/or hollow fiber region. 
     The overall arrangement and use of reinforcing components with respect to the catheter body and hollow fiber region, will be sufficient to permit the catheter, including distal hollow fiber region, to withstand the tensile, compressive and other such pressures, as well as flexing and other motions necessary to insert the catheter into tissue, preferably without the need for ancillary devices or measures, and removal of the catheter form the body tissue. 
     In a particularly preferred embodiment, the reinforcing component(s) can be selected from the group consisting of: 
     1) a safety wire attached proximate the distal end of a hollow fiber membrane and inside the distal end of the catheter body, thereby serving to further secure the hollow fiber membrane to the catheter body; 
     2) a relatively flexible, slotted, external support that substantially surrounds the hollow fiber membrane and, and in turn, serves to protect and strengthen it; 
     3) a relatively flexible inner lumen tube that extends substantially the length of the catheter and that defines a central lumen, and which serves to protect and strengthen it; 
     4) an inner support tube configured to have at least a single opening to facilitate the delivery of infusate through the hollow fiber membrane, the tube being mounted within the hollow fiber membrane, extending substantially the length of the hollow fiber membrane and defining a lumen and serves to strengthen the catheter. 
     In other preferred embodiments, the invention provides one or more features selected from the group consisting of an introducer (e.g., introducing catheter), steerability, and the ability to prime the catheter in the course of its use. 
     Although generally designed to be sufficiently rigid for insertion in its own right, a preferred catheter of the current invention can be used together with one or more ancillary components, such as an introducing catheter or introducer. 
     Similarly, a catheter of the present invention is, or can be adapted to be sufficiently steerable to permit the user to direct the distal end in vivo. Various approaches for imparting directional control to the distal tip will become apparent to those skilled in the art, given the present description, and are incorporated herein by reference. 
     As also described herein, a preferred catheter of this invention is adapted to be primed prior to use, in order to minimize air in the catheter prior to injection, which can interfere with infusate distribution. Suitable priming means and processes are described herein and will also be apparent to those skilled in the art, given the present description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 2A  is a lateral cross sectional view taken through lines  2 A- 2 A of  FIG. 1 . 
         FIG. 2B  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 1  taken through lines  2 B- 2 B of  FIG. 1 . 
         FIG. 3  is a plan view of the catheter of  FIG. 1 . 
         FIG. 4  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 5  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 4  taken through lines  5 - 5  of  FIG. 4 . 
         FIG. 6  is an external view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 7  is a plan view of the catheter of  FIG. 4 . 
         FIG. 8  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 9  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 8  taken through lines  9 - 9  of  FIG. 8 . 
         FIG. 10  is a plan view of the catheter of  FIG. 8 . 
         FIG. 11  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 12  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 11  taken through lines  12 - 12  of  FIG. 11 . 
         FIG. 13  is a plan view of the catheter of  FIG. 11 . 
         FIG. 14  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 15A  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 14  taken through the lines  15 A- 15 A. 
         FIG. 15B  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 14  taken through the lines  15 B- 15 B. 
         FIG. 15C  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 14  taken through the lines  15 C- 15 C. 
         FIG. 16  is a plan view of the catheter of  FIG. 14 . 
         FIG. 17  illustrates the infusate distribution pattern or plume of the catheter shown in  FIGS. 14-16 . 
         FIG. 18  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 19A  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 18  taken through the lines  19 A- 19 A. 
         FIG. 19B  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 18  taken through the lines  19 B- 19 B. 
         FIG. 19C  is a lateral cross sectional view of the infusion section of the catheter of  FIG. 14  taken through the lines  19 C- 19 C. 
         FIG. 20  is a plan view of the catheter of  FIG. 18 . 
         FIG. 21  illustrates the infusate distribution pattern or plume of the catheter shown in  FIGS. 18-20 . 
         FIG. 22  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 23  is a lateral cross sectional view of the catheter of  FIG. 22  taken through the lines  23 - 23 . 
         FIG. 24  is a plan view of the catheter of  FIG. 22 . 
         FIG. 25  illustrates the infusate diffusion pattern or plume of the catheter shown in  FIGS. 22-24 . 
         FIG. 26  is a view of the catheters of  FIGS. 14 and 18  attached to an infusion pump via a distribution manifold, in place during treatment through a human skull in to a cranial cavity following surgical resectioning of a tumor, showing the relative diffusion pattern of each catheter. 
         FIG. 27A  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 27B  is a lateral cross sectional view taken through lines  27 B- 27 B of  FIG. 17A . 
         FIG. 27C  is a view of the entire catheter of  FIG. 27A . 
         FIG. 27D  is a cross sectional view of a connector coupled to a removable stylet according to an embodiment of the present invention. 
         FIG. 28A  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 28B  is a lateral cross sectional view taken through lines  28 B- 28 B of  FIG. 28A . 
         FIG. 28C  is a view of the entire catheter of  FIG. 28A . 
         FIG. 29A  is a longitudinal cross sectional view of the infusion section of an embodiment of a catheter of the present invention. 
         FIG. 29B  is a lateral cross sectional view taken through lines  29 B- 29 B of  FIG. 29A . 
         FIG. 30A  is a plan view of an introducer used to introduce various embodiments of a catheter according to an embodiment of the present invention. 
         FIG. 30B  is a longitudinal cross sectional view of  FIG. 30A , taken along line  30 B- 30 B. 
         FIG. 30C  is a plan view of an introducer assembly including an introducer and a sheath according to an embodiment of the present invention. 
         FIG. 31  is a diagram of a valve assembly according to an embodiment of the present invention. 
         FIG. 32  is an illustration of the valve assembly of  FIG. 31  coupled with a syringe plunger apparatus according to an embodiment of the present invention. 
         FIGS. 33-35  are perspective views showing the attachment of a distal compression fitting according to an embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     The particulars shown herein are by way of example and for purposes of illustrative discussion of the invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for the fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice. 
     Selected Nomenclature 
     
         
           100  Catheter 
           110  Infusion Section 
           112  Catheter Body 
           112   a  Proximal End (Catheter Body) 
           112   b  Distal End (Catheter Body) 
           113  Lumen (Combined) 
           113   a  Lumen (Catheter Body) 
           113   b  Lumen (Hollow Fiber Membrane) 
           114  Hollow Fiber Membrane 
           114   a  Proximal End (Hollow Fiber Membrane) 
           114   b  Distal End (Hollow Fiber Membrane) 
           116  Safety Wire 
           118  Stylet 
           120  End Piece 
           122  Distal End 
           124  Connector 
           200  Catheter 
           210  Infusion Section 
           212  Catheter Body 
           212   a  Proximal End (Catheter Body) 
           212   b  Distal End (Catheter Body) 
           214  Hollow Fiber Membrane 
           214   a  Proximal End (Hollow Fiber Membrane) 
           214   b  Proximal End (Hollow Fiber Membrane) 
           216  External Support 
           218  Stylet 
           220  End Piece 
           222  Distal End 
           224  Connector 
           300  Catheter 
           310  Infusion Section 
           312  Catheter Body 
           312   a  Proximal End (Catheter Body) 
           312   b  Distal End (Catheter Body) 
           313  First Lumen 
           313   a  First Lumen (Catheter Body) 
           313   b  First Lumen (Hollow Fiber Membrane) 
           314  Hollow Fiber Membrane 
           314   a  Proximal End (Hollow Fiber Membrane) 
           314   b  Proximal End (Hollow Fiber Membrane) 
           315  Second Lumen 
           316  Inner Lumen Tube 
           318  Infusion Port 
           320  Distal End 
           324  Connector 
           326  Second Lumen Opening 
           400  Catheter 
           410  Infusion Section 
           412  Catheter Body 
           412   a  Proximal End (Catheter Body) 
           412   b  Distal End (Catheter Body) 
           413  Lumen 
           413   a  Lumen (Catheter Body) 
           413   b  Lumen (Hollow Fiber Membrane) 
           414  Hollow Fiber Membrane 
           414   a  Proximal End (Hollow Fiber Membrane) 
           414   b  Proximal End (Hollow Fiber Membrane) 
           416  Internal Support Tube 
           418  Stylet 
           420  End Piece 
           422  Distal End 
           424  Connector 
           500  Catheter 
           510  Infusion Section 
           512  Catheter Body 
           512   a  Proximal End (Catheter Body) 
           512   b  Distal End (Catheter Body) 
           513  Lumen 
           513   a  Lumen (Catheter Body) 
           513   b  Lumen (Hollow Fiber Membrane) 
           514  Hollow Fiber Membrane 
           514   a  Proximal End (Hollow Fiber Membrane) 
           514   b  Proximal End (Hollow Fiber Membrane) 
           516  Internal Support Tube 
           518  Stylet 
           520  End Piece 
           522  Distal End 
           524  Connector 
           600  Catheter 
           610  Infusion Section 
           612  Catheter Body 
           612   a  Proximal End (Catheter Body) 
           612   b  Distal End (Catheter Body) 
           613  Lumen 
           613   a  Lumen (Catheter Body) 
           613   b  Lumen (Hollow Fiber Membrane) 
           614  Hollow Fiber Membrane 
           614   a  Proximal End (Hollow Fiber Membrane) 
           614   b  Proximal End (Hollow Fiber Membrane) 
           616  Internal Support Tube 
           618  Stylet 
           620  End Piece 
           622  Distal End 
           624  Connector 
           700  Catheter 
           710  Infusion Section 
           712  Catheter Body 
           712   a  Proximal End (Catheter Body) 
           712   b  Distal End (Catheter Body) 
           713  First Lumen 
           714  Hollow Fiber Membrane 
           714   a  Proximal End (Hollow Fiber Membrane) 
           714   b  Proximal End (Hollow Fiber Membrane) 
           715  Second Lumen 
           716  Internal Support Tube 
           717  Open End (Delivery Tube) 
           718  Delivery Tube 
           719  Fluid Seal 
           720  End Piece 
           722  Distal End 
           724  Connector 
           800  catheter 
           810  infusion section 
           812  catheter body 
           812   a  proximal end 
           812   b  distal end 
           813  lumen 
           813   a  lumen 
           813   b  lumen 
           814  hollow fiber membrane 
           814   a  proximal end 
           814   b  distal end 
           819  fixed reinforcing stylet 
           820  end piece 
           824  fitting 
           831  fastener 
           900  catheter 
           910  infusion section 
           912  catheter body 
           912   a  proximal end 
           912   b  distal end 
           913  lumen 
           913   a  lumen 
           913   b  lumen 
           914  hollow fiber membrane 
           914   a  proximal end 
           914   b  distal end 
           916  internal support 
           917  removable priming tube 
           920  end piece 
           924  connector 
           1000  Infusion Pump 
           1100  catheter 
           1110  infusion section 
           1112  catheter body 
           1112   a  proximal end 
           1112   b  distal end 
           1113  lumen 
           1113   a  lumen 
           1113   b  lumen 
           1114  hollow fiber membrane 
           1114   a  proximal end 
           1114   b  distal end 
           1115  stylet 
           1115   b  distal end 
           1123  tip 
           1125  adhesive 
           1200  introducer 
           1202  needle 
           1202   a  proximal end 
           1202   b  distal end 
           1204  open tip 
           1206  hub 
           1208  vent plug 
           1210  locking portion 
           1212  sheath hub 
           1214  connector lock portion 
           1216  relief portion 
           1220  introducer assembly 
           1222  sheath 
           2000  syringe 
           2002  three-way valve 
           2004  two-way valve 
           2006  two-way valve 
           2008  three-way valve 
           2010  pressure transducer 
           2012  valve 
           2020  clamp 
           2022  pump 
           2024  flange 
           2026  clip 
           2027  holders 
           2028  lever 
           2030  plunger 
           2032  tubing holders 
           2034  bolus button 
           2040  nut 
           2042  catheter body 
           2044  ferrule 
           2046  receiving port 
         B Burr Hole 
         S Skull
 
Definitions
 
       
    
     “Catheter” is used in its general sense and refers to a conduit capable of transporting a substance or fluid to a remote location. 
     “Distal” means further from the point controlled by the operator (e.g., physician or technician) of a device. 
     “Fluid” means a substance offering no permanent resistance to change of shape, such as a gas or a liquid. 
     “Infusate” means medications and other substances which are beneficial to the healing process such as wound healing agents, pain medication and antibiotics. 
     “Proximal” means closer to the point controlled by the operator (e.g., physician or technician) of a device. 
     “Semi-Permeable Membrane” means a porous or semi-permeable barrier permitting controlled passage of fluid molecules under certain conditions. 
     “Therapeutic Fluid” means medications and other substances which are beneficial to the healing process such as wound healing agents, pain medication and antibiotics. 
     “Topical” means relating to a particular area at the surface and immediately underneath, such as an area exposed as the result of a wound. 
     “μm” means micron. 
     Construction 
       FIG. 1  is a longitudinal cross sectional view of the infusion section  110  of an embodiment of a catheter  100  of the present invention. An elongated catheter body  112  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  112   a , a distal end  112   b  and a lumen  113   a  capable of fluid communication, extending the length of the catheter body  112 . The infusion section  110  is defined by a hollow fiber membrane  114  which is attached to the distal end  112   b  of the catheter body  112  using a suitable medical grade adhesive such as epoxies or urethanes and defines a proximal end  114   a , a distal end  114   b  and a lumen  113   b . The lumen  113   b  of the hollow fiber membrane  114  is continuous with the lumen  113   a  of the catheter body  112  to form lumen  113  and allows fluid communication between the proximal end  112   a  of the catheter body  112  and the distal end  114   b  of the hollow fiber membrane  114 . A reinforcing component in the form of safety wire  116  is attached proximate the distal end  114   b  of the hollow fiber membrane  114  and inside the distal end  112   b  of the catheter body  112  and serves to further secure the hollow fiber membrane  114  to the catheter body  112 . An end piece  120  is attached to the distal end  114   b  of the hollow fiber membrane  114  and prevents the direct escape or intrusion of fluid from the lumen  113   b . The catheter  100  is designed to accommodate a removable stylet  118  through the lumen  113  which serves to stiffen the hollow fiber membrane  114  and catheter body  112 , thus facilitating introduction into a patient during treatment. The safety wire  116  also facilitates catheter  100  introduction into a patient and the removal of the stiffening stylet  118  prior to infusion and facilitating the save removal of the catheter  100  from the patient following completion of treatment. The end piece  120  therefore also provides a stop for the stylet  118  allowing it to sufficiently stiffen the infusion section  110  to be self-introducing into brain or other tissues. A self introducing catheter  100  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced backflow of therapeutic fluid during treatment due to less tissue compression between the catheter  100  and tissue resulting from direct introduction. 
       FIG. 2A  is a lateral cross sectional view taken through lines  2 A- 2 A of  FIG. 1  and illustrates the catheter body  112  defining the lumen  113   a . The stylet  118  is seen extending through the lumen  113   a . Similarly,  FIG. 2B  shows a lateral cross sectional view of the infusion section taken through lines  2 B- 2 B of  FIG. 1 , with the safety wire  116  and stylet  118  extending through the lumen  113   b .  FIG. 3  is a view of the entire catheter  100 , showing, inter alia, the connector  124  attached to the proximal end  112   a  of the catheter body  112 . 
       FIG. 4  shows the infusion section  210  of another embodiment of a catheter  200  of the present invention. An elongated catheter body  212  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  212   a  and a distal end  212   b  and a lumen  213   a  capable of fluid communication, extending the length of the catheter body  212 . The infusion section  210  is defined by a hollow fiber membrane  214  which is attached to the distal end  212   b  of the catheter body  212  using a suitable medical grade adhesive such as epoxies and urethanes and defines a proximal end  214   a , a distal end  214   b  and a lumen  213   b.  The lumen  213   b  of the hollow fiber membrane  214  is continuous with the lumen  213   a  of the catheter body  212  to form lumen  213  and allows fluid communication between the proximal end  212   a  of the catheter body  212  and the distal end  214   b  of the hollow fiber membrane  214 . A reinforcing component is provided in the form of relatively flexible, slotted, external support  216  made of polymers or metal surrounds the hollow fiber membrane  214  and serves to protect and strengthen the catheter  200 , thus facilitating catheter  200  introduction into a patient and facilitating the removal of the stiffening stylet  218  prior to infusion and facilitating the save removal of the catheter  200  from the patient following completion of treatment. The external support  216  may include other types of openings other than slots, such as circles or triangles as may be needed to create the appropriate, flexibility, strength and openness. Alternatively, the external support  216  can be fabricated from polymer or metallic wires to create a braided tube (not shown) having sufficient strength, openness and flexibility. An end piece  220  is attached to the distal end  214   b  of the hollow fiber membrane  214  and external support  216  and prevents the escape or intrusion of fluid from the lumen  213   b . The catheter  200  is designed to accommodate a removable stylet  218  through the lumen  213  which serves to significantly stiffen the catheter  200 , thus facilitating introduction into a patient during treatment. The end piece  220  therefore also provides a stop for the stylet  218  allowing it to sufficiently stiffen the catheter  200  to be self-introducing into brain or other tissues, thus relegating the need for a separate introducer. A self introducing catheter  200  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced backflow of therapeutic fluid during treatment due to less tissue compression between the catheter  200  and tissue resulting from direct introduction. 
       FIG. 5  is a lateral cross sectional view taken through infusion section  210  and illustrates the external support  216  surrounding the hollow fiber membrane  214  defining the lumen  213   b . The stylet  218  is seen extending through the lumen  213   a.    FIG. 6  shows an external view of the infusion section  210  including the external support  216 .  FIG. 7  is a view of the entire catheter  200 , showing, inter alia, the connector  224  attached to the proximal end  212   a  of the catheter body  212 . 
       FIG. 8  shows yet another embodiment of a catheter  300  of the present invention. An elongated catheter body  312  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  312   a , a distal end  312   b  and a lumen  313   a  capable of fluid communication, extending the length of the catheter body  312 . The infusion section  310  is defined by a hollow fiber membrane  314  which is attached to the distal end  312   b  of the catheter body  312  using a suitable medical grade adhesive such as epoxies or urethanes and defines a proximal end  314   a , a distal end  314   b  and a lumen  313   b . The lumen  313   b  of the hollow fiber membrane  314  is continuous with the lumen  313   a  of the catheter body  312  and allows fluid communication between the proximal end  312   a  of the catheter body  312  and the distal end  314   b  of the hollow fiber membrane  314 . A reinforcing component is provided in the form of relatively flexible inner lumen tube  316  which extends the length of the catheter  300  and defines a central lumen  315  and serves to provide a lumen to the distal end  326  of the catheter  300  and provide strength to the hollow fiber membrane  314  upon removal of instruments from the inner lumen tube  316  or removal of catheter from body tissue after treatment. The inner lumen tube  316  terminates at the distal end  320  at a distal lumen opening  326  thus allowing the catheter  300  to be additionally used for a removable stylet with a needle point (not shown) at the tip, projecting beyond opening  326 , for introduction of a catheter  300  into tissues requiring some cutting for ease of placement. After removing the needle point stylet (not shown), a removable anchoring wire (not shown) can be introduced through the inner lumen tube  316  to keep the catheter  300  from being displaced during drug infusion. The removable anchoring wire (not shown) could take various forms such that it can be passed down the inner lumen tube  316  and then deploys to an anchoring shape such as a hook (not shown) or spiral (not shown) shape. When removing the catheter  300  from tissue, the anchoring wire (not shown) would be pulled out of the tissue and then followed by the catheter  300  removal. Alternatively, for those applications not requiring anchoring, the inner tube lumen  316  could be used for the introduction of other medical instruments for tissue monitoring such as pressure or the aspiration of fluids. A self introducing catheter  300  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced reflux of therapeutic fluid during treatment due to less tissue compression between the catheter  300  and tissue resulting from direct introduction. 
       FIG. 9  is a lateral cross sectional view taken through infusion section  310  and illustrates the hollow fiber membrane  314 , the lumen  313   b , the internal support  316  and central lumen  315 .  FIG. 10  is a view of the entire catheter  300  showing, inter alia, the connector  324  attached to the proximal end  312   a  of the catheter body  312 . 
       FIG. 11  shows a further alternative embodiment of a catheter  400  of the present invention. An elongated catheter body  412  is made of any suitable flexible tubing material such as a medical grade urethane or other polymer and defines a proximal end  412   a , a distal end  412   b  and a lumen  413   a  capable of fluid communication, extending the length of the catheter body  412 . The infusion section  410  is defined by a hollow fiber membrane  414  which is attached to the distal end  412   b  of the catheter body  412  using a suitable medical grade adhesive such as epoxies and urethanes and defines a proximal end  414   a , a distal end  414   b  and a lumen  413   b . The lumen  413   b  of the hollow fiber membrane  414  is continuous with the lumen  413   a  of the catheter body  412  to form lumen  413  and allows fluid communication between the proximal end  412   a  of the catheter body  412  and the distal end  414   b  of the hollow fiber membrane  414 . A reinforcing component is provided in the form of an inner support tube  416  configured to have at least a single opening (not shown) to facilitate the delivery of infusate through the hollow fiber membrane  414  and is mounted within the hollow fiber membrane  414 , extends the length of the hollow fiber membrane  414  and defines a lumen  413   b  and serves to strengthen the catheter  400 , thus facilitating catheter  400  introduction into a patient and facilitating the removal of the stiffening stylet  418  prior to infusion and facilitating the save removal of the catheter  400  from the patient following completion of treatment. The internal support  416  may include other types of openings other than a single hole, such as circles, slots or triangles as may be needed to create the appropriate, flexibility, strength and openness. Alternatively, the internal support  416  can be fabricated from polymer or metallic wires to create a braided tube (not shown) having sufficient strength, openness and flexibility. The catheter  400  is designed to accommodate a removable stylet  418  through the lumen  413  which serves to significantly stiffen the infusion section  410 , thus facilitating introduction into a patient during treatment. An end piece  420  is attached to the distal end  414   b  of the hollow fiber membrane  414  and prevents the direct escape or intrusion of fluid from the lumen  413 . A self introducing catheter  400  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced reflux of therapeutic fluid during treatment due to less tissue compression between the catheter  400  and tissue resulting from direct introduction. 
       FIG. 12  is a lateral cross sectional view taken through infusion section  410  and illustrates the hollow fiber membrane  414 , the lumen  413   b , the internal support  416  and removable stylet  418 .  FIG. 13  is a view of the entire catheter  400  showing, inter alia, the connector  424  attached to the proximal end  412   a  of the catheter body  412 . 
       FIG. 14  shows an additional embodiment of a catheter  500  of the present invention. An elongated catheter body  512  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  512   a , a distal end  512   b  and a lumen  513   a  capable of fluid communication, extending the length of the catheter body  512 . The infusion section  510  is defined by a hollow fiber membrane  514  which is attached to the distal end  512   b  of the catheter body  512  using a suitable medical grade adhesive such as epoxies and urethanes and defines a proximal end  514   a , a distal end  514   b  and a lumen  513   b . The lumen  513   b  of the hollow fiber membrane  514  is continuous with the lumen  513   a  of the catheter body  512  to form lumen  513  and allows fluid communication between the proximal end  512   a  of the catheter body  512  and the distal end  514   b  of the hollow fiber membrane  514 . A reinforcing component is provided in the form of inner support tube  516  and is configured to have at least a single opening (not shown) to facilitate the delivery of infusate through the hollow fiber membrane and is mounted within the hollow fiber membrane  514 , extends the length of the hollow fiber membrane  514  and defines a lumen  513   b  and serves to strengthen the catheter  500 , thus facilitating catheter  500  introduction into a patient during treatment and upon removing the stiffening stylet  518  prior to infusion or upon removing the catheter  500  from the patient following completion of treatment. The internal support  516  may include other types of openings other than a single hole, such as circles, slots or triangles as may be needed to create the appropriate, flexibility, strength and openness. Alternatively, the internal support  516  can be fabricated from polymer or metallic wires to create a braided tube (not shown) having sufficient strength, openness and flexibility. The catheter  500  is designed to accommodate a removable stylet  518  through the lumen  513  which serves to significantly stiffen the infusion section  510  and catheter body  512 , thus facilitating introduction into a patient during treatment. An end piece  520  is attached to the distal end  514   b  of the hollow fiber membrane  514  and prevents the escape or intrusion of fluid from the lumen  513 . A self introducing catheter  500  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced reflux of therapeutic fluid during treatment due to less tissue compression between the catheter  500  and tissue resulting from direct introduction. 
       FIG. 15A  is a lateral cross sectional view taken infusion section  510  and illustrates the hollow fiber membrane  514 , the lumen  513   b , the internal support  516  and removable stylet  518 .  FIG. 15B  is a lateral cross sectional view taken infusion section  510  and illustrates the hollow fiber membrane  514 , the lumen  513   b , the internal support  516  and removable stylet  518 .  FIG. 15C  is a lateral cross sectional view taken infusion section  510  and illustrates the hollow fiber membrane  514 , the lumen  513   b , the internal support  516  and removable stylet  518 . It is noted that the hollow fiber membrane  514  becomes progressively thicker in a distal direction as illustrated in  FIGS. 15A-15C . Not shown specifically, it is noted that the hollow fiber membrane  514  becomes symmetrically progressively thicker in a proximal direction as seen in  FIG. 14 .  FIG. 16  is a view of the entire catheter  500  showing, inter alia, the connector  524  attached to the proximal end  512   a  of the catheter body  512 . It should also be mentioned that while not shown, the invention contemplates and therefore is within the scope of a non-symmetrically and non-uniformly tapered hollow fiber membrane  514 .  FIG. 16  is a view of the entire catheter  400  showing, inter alia, the connector  524  attached to the proximal end  512   a  of the catheter body  512 . 
       FIG. 17  illustrates the infusate distribution pattern or plume of the infusion section  510  of catheter  500  shown in  FIGS. 14-16 . It is noted that the thinnest section of the hollow fiber membrane  514  as illustrated in  FIG. 15A , represents the furthest point of infusate distribution from the hollow fiber membrane  514  while the closest point of infusate distribution corresponds with the thickest section of hollow fiber membrane  514 , as illustrated in  FIG. 15C . The intermediate section of hollow fiber membrane  514  represents an intermediate point of infusate distribution, as illustrated in  FIG. 15B . The reason for this distribution pattern is that the thinner sections of the hollow fiber membrane  514  offer less resistance to the outflow of infusate and thus increases the flow at these reduced resistance regions along the length of the hollow fiber membrane  514 . One of the advantages conferred by using hollow fiber membrane technology is that while the infusate will distribute further through a thinner section, the infusate is released along the length of the hollow fiber membrane at similar pressures creating a reliable distribution pattern. In some instances, anatomy targeted for treatment may be more effective with an infusate distribution pattern which more closely fits the shape of the tissue targeted for treatment. One example is tumors which tend to be more spherical in shape and thus the ideal drug distribution pattern would be greater at the center of the hollow fiber membrane  514  and decreases towards each end. 
       FIG. 18  shows another embodiment of a catheter  600  of the present invention. An elongated catheter body  612  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  612   a , a distal end  612   b  and a lumen  613   a  capable of fluid communication, extending the length of the catheter body  612 . The infusion section  610  is defined by a hollow fiber membrane  614  which is attached to the distal end  612   b  of the catheter body  612  using a suitable medical grade adhesive such as epoxies or urethanes and defines a proximal end  614   a , a distal end  614   b  and a lumen  613   b . The lumen  613   b  of the hollow fiber membrane  614  is continuous with the lumen  613   a  of the catheter body  612  to form lumen  613  and allows fluid communication between the proximal end  612   a  of the catheter body  612  and the distal end  614   b  of the hollow fiber membrane  614 . A reinforcing component is provided as an inner support tube  616  configured to have at least a single opening (not shown) to facilitate the delivery of infusate through the hollow fiber membrane  614  and is mounted within the hollow fiber membrane  614 , extends at least the length of the hollow fiber membrane  614  and defines a lumen  613   b  and serves to strengthen the hollow fiber membrane  614 , thus facilitating introduction into a patient during treatment and upon removing the stiffening stylet  618  prior to infusion or upon removing catheter  600  from the patient following completion of treatment. The internal support  616  may include other types of openings other than a single hole, such as circles, slots or triangles as may be needed to create the appropriate flexibility, strength and openness. Alternatively, the internal support  616  can be fabricated from polymer or metallic wires to create a braided tube (not shown) having sufficient strength, openness and flexibility. The catheter  600  is designed to accommodate a removable stylet  618  through the lumen  613  which serves to significantly stiffen the infusion section  610 , thus facilitating catheter  600  introduction into a patient during treatment. An end piece  620  is attached to the distal end  614   b  of the hollow fiber membrane  614  and prevents the escape or intrusion of fluid from the lumen  613 . A self introducing catheter  600  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced reflux of therapeutic fluid during treatment due to less tissue compression between the catheter  600  and tissue resulting from direct introduction. 
       FIG. 19A  is a proximal lateral cross sectional view taken through infusion section  610  and illustrates the hollow fiber membrane  614 , the lumen  613   b , the internal support  616  and removable stylet  618 .  FIG. 19B  is an intermediate lateral cross sectional view taken through infusion section  610  and illustrates the hollow fiber membrane  614 , the lumen  613   b , the internal support  616  and removable stylet  618 .  FIG. 19C  is a distal lateral cross sectional view taken through infusion section  610  and illustrates the hollow fiber membrane  614 , the lumen  613   b , the internal support  616  and removable stylet  618 . It is noted that the hollow fiber membrane  614  becomes progressively thinner in a distal direction as illustrated in  FIGS. 19A-19C .  FIG. 20  is a view of the entire catheter  600  showing, inter alia, the connector  624  attached to the proximal end  612   a  of the catheter body  612 . It should also be mentioned that while not shown, the invention contemplates and therefore is within the scope of a non-symmetrically and non-uniformly tapered hollow fiber membrane  614 . 
       FIG. 21  illustrates the infusate distribution pattern or plume of the hollow fiber section  614  catheter  600  shown in  FIGS. 18-20 . It is noted that the thickest section of the hollow fiber membrane  614  as illustrated in  FIG. 19A , represents the closest point of infusate distribution from the hollow fiber membrane  614  while the furthest point of infusate distribution from the hollow fiber membrane  614  corresponds with the thinnest section of hollow fiber membrane  614 , as illustrated in Fig,  19 C. The intermediate section of hollow fiber membrane  614  represents an intermediate point of infusate distribution, as illustrated in  FIG. 19B . The reason for this is that the thinner sections of the hollow fiber membrane  614  offer less resistance to the outflow of infusate and thus increases the flow at the reduced resistance regions along the length of the hollow fiber membrane  614 . In some instances treatment of anatomy targeted for treatment may be more effective with a varying infusate distribution pattern. 
       FIG. 22  shows still another embodiment of a catheter  700  of the present invention. An elongated catheter body  712  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  712   a  and a distal end  712   b . The infusion section  710  is defined by a hollow fiber membrane  714  which is attached to the distal end  712   b  of the catheter body  712  using a suitable medical grade adhesive such as epoxies and urethanes and defines a proximal end  714   a , and a distal end  714   b . A reinforcing component is provided as an inner support tube  716  and is configured to have at least a single opening (not shown) to facilitate the delivery of infusate through the hollow fiber membrane  714 , is mounted within the hollow fiber membrane  714 , extends the length of the hollow fiber membrane  714 , defines a first lumen  713  and serves to strengthen the infusion section  710  and catheter body  712 , thus facilitating catheter  700  introduction into a patient during treatment and upon removing the stiffening stylet (not shown) prior to infusion or upon removing the catheter  700  from the patient following completion of treatment. The internal support  716  may include other types of openings other than a single hole, such as circles, slots or triangles as may be needed to create the appropriate, flexibility, strength and openness. Alternatively, the internal support can be fabricated from polymer or metallic wires to create a braided tube (not shown) having sufficient strength, openness and flexibility. The catheter  700  also has a flexible delivery tube  718  which is placed in the catheter after removing the removal stylet (not shown) defining a second lumen  715  extending through the first lumen  713  and along the length of the catheter  700  which serves to deliver infusate to the distal end  714   b  of the hollow fiber membrane  714 . An end piece  720  is attached to the distal end  714   b  of the hollow fiber membrane  714  and prevents the direct escape or intrusion of fluid from the first lumen  713 . A fluid seal  719  such as a Touhy Borst at the proximal end  712   a  of the catheter body  712  creates a sealed chamber (unnumbered) defined by the first lumen  713 . A self introducing catheter  700  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced reflux of therapeutic fluid during treatment due to less tissue compression between the catheter  700  and tissue resulting from direct introduction. 
       FIG. 23  is a lateral cross sectional view taken through infusion section  710  and illustrates the hollow fiber membrane  714 , first lumen  713 , internal support  716 , delivery tube  718  and second lumen  715 .  FIG. 24  is a view of the entire catheter  700  showing, inter alia, the connector  724  attached to the proximal end (unnumbered) of the delivery tube  718 . 
       FIG. 25  illustrates the infusate distribution pattern or plume of the hollow fiber section  714  catheter  700  shown in  FIGS. 22-24 . It is noted that in this embodiment the hollow fiber membrane  714  has a substantially consistent diameter and thickness and that the region of furthest infusate distribution from the hollow fiber membrane  714  is most distal with the distribution becoming less from the hollow fiber membrane  714  in a proximal direction. The reason for this is that infusate is delivered by positive fluid pressure along the length of the catheter  700  via the second lumen  715  of the delivery tube  718  before emptying from the open end  717  into the first lumen  713 . When the first lumen  713  is filled with infusate and after closing the fluid seal  719 , the infusate will be forced first through the internal support  716  openings (not shown), then through the pore structure of the hollow fiber membrane  714  into the tissue of the patient to be treated. One of the effects of the hollow fiber membrane  714  is to substantially equalize the pressure along the length of the infusion section  710  at which the infusate is distributed to the patient. Because in this embodiment the open end  717  of the delivery tube  718  is located relatively distally, the infusate will exit the infusion section  710  at the maximum distance from the hollow fiber membrane  714 . The first lumen  713  in the region of the hollow fiber membrane  714  is sufficiently small such as to create flow resistance with lumen pressure increasing from the distal region (unnumbered) to the proximal region (unnumbered) of the hollow fiber  714 . This pressure drop creates the distribution pattern as represented in  FIG. 25  with increased distribution at the distal region (unnumbered) of the hollow fiber membrane  714  due to the highest infusate pressure there. 
       FIG. 26  illustrates the deployment of the catheters  100 ,  200 ,  600  in an array to effectively cover the region closest to the brain cavity created by surgical resection of a brain tumor. It is seen that the catheters  100 ,  200 ,  600  are connected and in fluid communication with separate infusion pumps  1000 . Alternatively, catheters  300 ,  400  could replace catheters  100 ,  200  to provide a similar infusate distribution plume. 
       FIG. 27A  is a longitudinal cross sectional view of the infusion section  810  of an embodiment of a catheter  800  of the present invention. An elongated catheter body  812  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers or metals and defines a proximal end  812   a , a distal end  812   b  and a lumen  813   a  capable of fluid communication, extending the length of the catheter body  812 . The infusion section  810  is defined by a hollow fiber membrane  814  which is attached to the distal end  812   b  of the catheter body  812  using a suitable medical grade adhesive such as epoxies or urethanes and defines a proximal end  814   a,  a distal end  814   b  and a lumen  813   b . The lumen  813   b  of the hollow fiber membrane  814  is continuous with the lumen  813   a  of the catheter body  812  to form lumen  813  and allows fluid communication between the proximal end  812   a  of the catheter body  812  and the distal end  814   b  of the hollow fiber membrane  814 . An end piece  820  is attached to the distal end  814   b  of the hollow fiber membrane  814  and prevents the direct escape or intrusion of fluid from the lumen  813   b.    
     The catheter  800  is designed to accommodate a fixed reinforcing stylet  819  through the lumen  813  which serves to stiffen the hollow fiber membrane  814  and catheter body  812 , thus facilitating introduction into a patient during treatment. The stylet  819  can comprise any suitable material to provide stiffness to the hollow fiber membrane  814 . For example, in certain embodiments the stylet  819  may comprise nickel titanium or nitinol. The end piece  820  therefore also provides a stop. In certain embodiments the stylet  819  provides a steering advantage for the catheter  800 . For example, the stylet  819  can be subjected to torque by the user, upon application of rotational force upon a fitting  824  (see  FIG. 27D ) at the proximal end of the stylet  819 . To improve steerability, the stylet  819  may be tapered to provide different stiffnesses along the catheter length and/or the stylet tip can be shaped in a variety of curved configurations. Accordingly, the stylet  819  and catheter  800  can be guided through a tissue mass or fluid filled organ. A self introducing catheter  800  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced backflow of therapeutic fluid during treatment due to less tissue compression between the catheter  800  and tissue resulting from direct introduction. 
       FIG. 27B  is a lateral cross sectional view taken through lines  27 B- 27 B of  FIG. 17A  and illustrates the catheter body  812  defining the lumen  813   a . The stylet  819  is seen extending through the lumen  813   a .  FIG. 27C  is a view of the entire catheter  800 , showing, inter alia, a fitting  824  attached to the proximal end  812   a  of the catheter body  812 .  FIG. 27D  is a cross sectional view of the fitting  824  coupled to the stylet  819  with a fastener  831 . The stylet  819  can also be fastened to the center of the fitting  824  concentrically with the lumen  813   a  to provide improved rotational control. A user can apply a rotational force to the fitting  824  to supply a torsional force to the stylet  819  via the fastener  831 . 
       FIG. 28A  is a longitudinal cross sectional view of the infusion section  910  of an embodiment of a catheter  900  of the present invention. An elongated catheter body  912  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers and defines a proximal end  912   a , a distal end  912   b  and a lumen  913   a  capable of fluid communication, extending the length of the catheter body  912 . The infusion section  910  is defined by a hollow fiber membrane  914  which is attached to the distal end  912   b  of the catheter body  912  using a suitable medical grade adhesive such as epoxies or urethanes and defines a proximal end  914   a , a distal end  914   b  and a lumen  913   b . The lumen  913   b  of the hollow fiber membrane  914  is continuous with the lumen  913   a  of the catheter body  912  to form lumen  913  and allows fluid communication between the proximal end  912   a  of the catheter body  912  and the distal end  914   b  of the hollow fiber membrane  914 . A reinforcing component is provided in the form of relatively flexible, slotted, internal support  916  made of polymers or metal within the hollow fiber membrane  914  that serves to protect and strengthen the catheter  900 , thus facilitating catheter  900  introduction into a patient and facilitating the removal of a removable priming tube  917  prior to infusion and facilitating the safe removal of the catheter  900  from the patient following completion of treatment. The internal support  916  may include other types of openings other than slots, such as circles or triangles as may be needed to create the appropriate, flexibility, strength and openness. Alternatively, the internal support  916  can be fabricated from polymer or metallic wires to create a braided tube (not shown) having sufficient strength, openness and flexibility. 
     An end piece  920  is attached to the distal end  914   b  of the hollow fiber membrane  914  and prevents the direct escape from or intrusion of fluid into the lumen  913   b . The catheter  900  is designed to accommodate a removable priming tube  917  through the lumen  913  which serves to prime the catheter  900  prior to infusion, and also stiffen the hollow fiber membrane  914  and catheter body  912 , thus facilitating introduction into a patient during treatment. An optional, removable stylet may be inserted within the priming tube  917  to provide extra stiffness during introduction of the catheter  900 . The optional stylet can then be removed prior to priming with the priming tube  917 . The priming tube  917  also facilitates catheter  900  introduction into a patient, the removal of the priming tube  917  prior to infusion, and the safe removal of the catheter  900  from the patient following completion of treatment. The end piece  920  therefore also provides a stop for the priming tube  917  allowing it to sufficiently stiffen the infusion section  910  to be self-introducing into brain or other tissues. A self introducing catheter  900  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced backflow of therapeutic fluid during treatment due to less tissue compression between the catheter  900  and tissue resulting from direct introduction. 
       FIG. 28B  is a lateral cross sectional view taken through lines  28 B- 28 B of  FIG. 28A  and illustrates the catheter body  912  defining the lumen  913   b . The priming tube  917  is seen extending through the lumen  913   b . The internal support  916  is seen defining the lumen  913   b  along with the hollow fiber membrane  914 .  FIG. 28C  is a view of the entire catheter  900 , showing, inter alia, the connector  924 , with an infusate visualization feature, attached to the proximal end  912   a  of the catheter body  912 . Although not shown in  FIG. 28C , the priming tube  917  can be inserted within lumen  913 , and can include a fitting or connector at its proximal end for infusion connection. 
       FIG. 29A  is a longitudinal cross sectional view of the infusion section  1110  of an embodiment of a catheter  1100  of the present invention. An elongated catheter body  1112  is made of any suitable flexible tubing material such as a medical grade urethane or other polymers or metals and defines a proximal end  1112   a , a distal end  1112   b  and a lumen  1113   a  capable of fluid communication, extending the length of the catheter body  1112 . The infusion section  1110  is defined by a hollow fiber membrane  1114  which is attached to the distal end  1112   b  of the catheter body  1112  using a suitable medical grade adhesive such as epoxies or urethanes and defines a proximal end  1114   a , a distal end  1114   b  and a lumen  1113   b . The lumen  1113   b  of the hollow fiber membrane  1114  is continuous with the lumen  1113   a  of the catheter body  1112  to form lumen  1113  and allows fluid communication between the proximal end  1112   a  of the catheter body  1112  and the distal end  1114   b  of the hollow fiber membrane  1114 . The catheter  1100  is designed to accommodate a includes a stylet  1115  through the lumen  1113  which serves to stiffen the hollow fiber membrane  1114  and catheter body  1112 . The stylet  1115  also facilitates catheter  1100  introduction into a patient and the safe removal of the catheter  1100  from the patient following completion of treatment. 
     The stylet  1115  includes a tip  1123  attached to the distal end  1115   b  of the stylet  1115 . The tip  1123  may be formed integrally with the stylet  1115 , or formed separately and then attached. The tip  1123  and distal end  1115   b  of the stylet  1115  are fastened to the distal end  1114   b  of the hollow fiber membrane  1114  with an adhesive  1125 . The stylet  1115  can thus sufficiently stiffen the infusion section  1110  to be self-introducing into brain or other tissues. In addition, the tip  1123  prevents the direct escape from or intrusion of fluid into the lumen  1113   b . The tip  1123  can take a number of forms. In one embodiment the tip  1123  is formed in a ball or spherical shape. Accordingly, the round front side of the tip  1123  can facilitate the self introduction of the catheter  1100 . A self introducing catheter  1100  is advantageous for several reasons: (1) the procedure can be completed in less time; (2) the likelihood of infection is reduced due to fewer required instruments; and (3) reduced backflow of therapeutic fluid during treatment due to less tissue compression between the catheter  1100  and tissue resulting from direct introduction. 
       FIG. 29B  is a lateral cross sectional view taken through lines  29 B- 29 B of  FIG. 29A  and illustrates the hollow fiber membrane  1114  defining the lumen  1113   b.    
       FIG. 30A  is a plan view of an introducer  1200  used to introduce various embodiments of the catheter  100 ,  200 ,  300 ,  400 ,  500 ,  600 ,  700 ,  800 ,  900 ,  1100  into a brain or other tissues according to certain embodiments of the invention. While in certain embodiments a catheter of the invention may be self-introduced without the introducer  1200 , in certain embodiments the introducer  1200  can also be used to ease insertion. The introducer  1200  includes a needle  1202  extending between a proximal end  1202   a  and a distal end  1202   b . The needle  1202  can comprise stainless steel and includes an open tip  1204  at the distal end  1202   b  providing access to an inner lumen of the needle. At the proximal end  1202   a , the needle is coupled with a hub  1206 . The hub  1206  includes a vent plug  1208  at its proximal end, which is adapted to receive one of the various embodiments of the catheter of the invention. The introducer  1200  can be used alone or in conjunction with a sheath, as shown in  FIG. 30C . 
       FIG. 30B  is a longitudinal cross sectional view of  FIG. 30A , taken along line  30 B- 30 B. The hub  1206  includes a locking portion  1210  that can secure the hub  1206  to a sheath hub  1212  as shown in  FIG. 30C . The hub  1206  includes a connector lock portion  1214  to secure the catheter connector to the hub  1206  in some embodiments. As shown in  FIG. 30B , the hub  1206  also includes a relief portion  1216 , which can guide insertion of the catheter into the needle lumen. 
       FIG. 30C  is a plan view of an introducer assembly  1220  including the introducer  1200  coupled to the sheath hub  1212 , with a sheath  1222  coupled to the sheath hub about the needle  1202  of introducer. The sheath hub  1212  can secure the sheath  1222  in place as the catheter is introduced into the adjacent tissue. 
     In certain embodiments, the sheath  1222  comprises a “tear-away” plastic sheath placed over the needle  1202 . Accordingly, in some cases the introducer  1200  comprises a sterile disposable introducer that provides an access to a targeted muscle or other tissue compartment to facilitate the placement of catheters according to embodiments of the invention. According to some embodiments, in a first step, the sharp-tipped needle  1202  and sheath  1222  are inserted through the skin and into the targeted tissue compartment. Once properly positioned, the needle  1202  is removed leaving the hollow tear-away sheath  1222  in place. One of the various catheters provided in embodiments of the invention can then be placed through the hollow sheath  1222  and into the tissue compartment. Once the catheter is placed, the sheath  1222  is designed to easily tear away for removal. In some cases the needle  1202  and sheath  1222  are similar in respects to those used for cardiovascular or percutaneous access devices. For example, the sheath  1222  can comprise a thin walled polyethylene tubing. The introducer  1200  can comprise a stainless steel needle  1202  with a three-facet sharp tip point  1204 . 
     Use 
     Using the various embodiments of the catheter of the present invention following the creation of a burr hole B in the patient&#39;s skull S involves initially introducing the catheter into tissue through the burr hole B to the treatment site, then removing the stylet. This is followed by inserting a priming tube such as delivery tube  718  having a similar outer dimension as the removable stylet into the lumen and priming the catheter under pressure with infusate. This procedure is necessary to remove air and other gases from the catheter prior to initiating treatment. In some embodiments, a priming tube such as tube  917  can serve to introduce the catheter without a separate stylet, and then be used to prime the catheter. In the case of the catheter  300 , the infusion port  318  is filled with infusate prior to introducing the catheter  300  and capped. The priming tube is next removed while infusing the priming tube for some catheters to insure no additional air is introduced into the catheter during priming tube removal. Using the connector the catheter is attached to an infusion pump  1000  which provides a controlled amount of positive fluid pressure, causing the infusate to be distributed through the hollow fiber. Following completion of the procedure, the catheter is disconnected from the infusion pump  1000 , removed from the treatment site and disposed of. 
     EXAMPLE 1 
     Infusion Procedure for Pig Brain MRI Contrast Study 
     Materials and Methods 
     Pretest Setup with Pressure Monitoring 
     
         
         1.1 Fill a 10 ml syringe  2000  ( FIG. 31 ) with the desired infusate mixture. Connect a three-way valve  2002  to the 10 ml syringe with the T of the three-way valve pointing up. Connect a two-way valve  2004  off of the straight section of the three-way valve. 
         1.2 Going up from the three way valve  2002  attach a two-way valve  2006 , then another three-way valve  2008 , valve 4, then an Edwards Lifesciences PX600 pressure transducer  2010  with valve  2012  on the transducer positioned on the top ( FIG. 31 ). 
         1.3 Connect a Medex 536040 line to valve  2008 , leave the other end open, it will later be attached to the BC Biomedical pressure monitor. Attach the cord from the pressure transducer  2010  to the Twin Star pressure monitor ( FIG. 31 ). 
         1.4 Connect a Medex 536040 line to valve  2004  ( FIG. 31 ). Leave the end of the tubing that is to connect to the catheter open for now. 
         1.5 Lift the syringe barrel clamp  2020  and slide the syringe  2000  and valve assembly into the slot on the top of the pump  2022  ( FIG. 32 ). 
         1.6 Place the flange  2024  of the syringe  2000  into the syringe barrel flange clip  2026  to secure the syringe ( FIG. 32 ). 
         1.7 Open the syringe plunger holders  2027  by squeezing the syringe plunger  2030  release lever  2028 , slide the plunger holders over until they are flush with the plunger  2030  of the syringe and then release the syringe plunger holders to secure the plunger  2030  in place ( FIG. 32 ). 
         1.7.1 Run the tubing through the tubing holders  2032  to secure the tubing to the pump ( FIG. 32 ). 
         1.8 Record the date, start time, fiber length, infusion rate, lot number, and catheter number in the test setup of each catheter being tested. 
         1.9 Prime all of the lines, fittings, and valves using the bolus button  2034  on the pump  2022 . Press and hold the bolus button  2034  with all of the valves open. When infusate comes out of valve  2012  close valve  2012 . When it comes out of the end of the tubing attached to valve  2008  attach the line to the BC Biomedical pressure monitor, be sure that the BC Biomedical pressure monitor is filled with fluid before connecting. Continue to hold the bolus button  2034  until infusate is coming out of the line attached to valve  2004  ( FIG. 31 ). 
         1.10 While holding the end of the line coming from tubing holders even with the pressure transducer zero the pressure monitors. After zeroing the monitors close valve  2012 .
 
Pretest Setup without Pressure Monitoring
 
         2.1 Fill a 10 ml syringe with the desired infusate mixture. 
         2.2 Connect a Medex 536040 line to the syringe. Leave the end of the tubing that is to connect to the catheter open for now. 
         2.3 Lift the syringe barrel clamp and slide the syringe into the slot on the top of the pump ( FIG. 32 ). 
         2.4 Place the flange of the syringe into the syringe barrel flange clip to secure the syringe ( FIG. 32 ). 
         2.5 Open the syringe plunger holders by squeezing the syringe plunger release lever, slide the plunger holders over until they are flush with the plunger of the syringe and then release the syringe plunger holders to secure the plunger in place ( FIG. 32 ). 
         2.6 Run the tubing through the tubing holders to secure the tubing to the pump ( FIG. 32 ). 
         2.7 Record the date, start time, fiber length, infusion rate, lot number, and catheter number in the test setup of each catheter being tested. 
         2.8 Prime the line by pressing and holding the bolus button. Continue to hold the bolus button until infusate is coming out of the luer fitting.
 
4 Step Catheter Placement
 
Step 1: Catheter Insertion
 
         3.1 Insert the priming tube completely into the catheter. 
         3.2 If using the optional support stylet for superior positioning, insert the support stylet into the priming tube completely and connect the luer fittings. 
         3.3 Insert the catheter into the brain and guide the hollow fiber on the distal end of the catheter to the desired region of the brain. 
         3.4 Secure the catheter so that it is not moved during the priming, tunneling, or infusion process. 
         3.5 Remove the support stylet from the priming tube (if used in step 3.2). It is important to follow catheter priming procedure to prevent air bubbles in the catheter. In addition, it is important to maintain prime and no air bubbles in catheter and infusion lines during catheter insertion, tunneling and fitting attachment.
 
Step 2: Priming the Catheter
 
         4.1 Attach a syringe filled with infusate to the male/female luer fitting attached to the priming tube. 
         4.2 Unlock the priming tube luer fitting from the female/female connector luer fitting attached to the catheter body. 
         4.3 Inject infusate at a steady rate into the catheter through the priming tube until the level of the infusate reaches luer fitting at the proximal end of the catheter body. 
         4.4 Continue to rapidly inject infusate while pulling the priming tube out of the catheter body. The female/female luer fitting should be full when the priming tube is removed.
 
Step 3: Tunneling the Catheter
 
         5.1 Cut off the proximal luer fitting from the catheter body with a scissors and discard the luer fitting. 
         5.2 Attach the small tipped trocar to the proximal end of the catheter body. 
         5.3 Tunnel the catheter subcutaneously for several cm from the entry point. 
         5.4 After tunneling the catheter cut off the trocar from the catheter body with a scissors.
 
Step 4: Attaching the Distal Compression Fitting
 
         6.1 Slide the flangeless nut  2040  over the catheter body  2042 , with the nut threads facing proximally ( FIG. 33 ). 
         6.2 Slip the ferrule  2044  over the catheter body, with the tapered portion of the ferrule facing toward the nut ( FIG. 34 ). 
         6.3 Insert the tubing with the ferrule in place into the receiving port  2046 , and, while holding the tubing down firmly into the port, tighten the receiving port onto the nut finger tight ( FIG. 35 ). 
         6.4 Remove the nut and confirm that the proximal end of the catheter is flush with the top of the ferrule. Any excess of the catheter tubing could lead to leaking from the fitting. Cut off any excess flush with the ferrule. 
         6.5 Retighten the red receiving port onto the nut. 
         6.6 Fill the nut with luer attachment with infusate; be sure that there are no air bubbles in the system. 
         6.7 Attach the line from the tubing holders to the luer fitting on the red nut. Both fittings should be completely filled with infusate so no air is entrapped in the catheter.
 
Running the Infusion with Pressure Monitoring
 
         7.1 Set the flow rate on the infusion pump. 
         7.2 Start the infusion pump, then the pressure monitors and a timer immediately after. 
         7.3 Observe the pressures being recorded. If the catheter is not building any pressure check and tighten fittings that may be leaking 
         7.4. If pump and monitors are to be removed for MRI images, press stop on the pump, options, choose option one—standby and after entering an adequate amount of time press enter and then complete step 7.4.1 to 7.4.5. 
         7.4.1 Close valves  2004  and  2006  ( FIG. 31 ). 
         7.4.2 Disconnect valve  2008  from valve  2006 . Remove the tubing from the tubing holders  2002  ( FIG. 32 ). 
         7.4.3 Release the syringe plunger holders and slide the syringe plunger release lever out of the way. 
         7.4.4 Pull up on the syringe barrel clamp and carefully remove the syringe flange from the syringe barrel flange clip ( FIG. 32 ). Place the syringe and tubing in the coil with the gel container and take images as needed. 
         7.4.5 To reattach the syringe and continue to infuse follow steps 1.5 to 1.8, then reattach valve  2006  to valve  2008 , be sure that no air is allowed into the system. Open valves  2004  and  2006  and press start on the pump ( FIG. 31 ).
 
Running the Infusion without Pressure Monitoring
 
         8.1 Set the flow rate on the infusion pump. 
         8.2 Start the infusion pump, then a timer immediately after. 
         8.3. If pump is to be removed for MRI images, press stop on the pump, options, choose option one—standby and after entering an adequate amount of time press enter then follow steps 8.3.1 to 8.3.4. 
         8.3.1 Remove the tubing from the tubing holders ( FIG. 31 ). 
         8.3.2 Release the syringe plunger holders and slide the syringe plunger release lever out of the way. 
         8.3.3 Pull up on the syringe barrel clamp and carefully remove the syringe flange from the syringe barrel flange clip ( FIG. 32 ). Place the syringe and tubing in the coil with the gel container and take images as needed. 
         8.3.4 To reattach the syringe and continue to infuse follow steps 1.5 to 1.8 and press start on the pump ( FIG. 31 ). 
       
    
     Experimental Protocol 
     A tumor infusion animal (porcine) study was performed using a system as described herein. Burr holes were created on both the left and right sides of the skull, burr holes were 1 cm deep. A Vygon™ catheter was placed on the left side and inserted 3 cm from the skull surface. The Vygon™ catheter was primed with a syringe as it would be in a standard surgical procedure. The Vygon catheter was then tunneled through the scalp. A polycarbonate plate was secured to the skull with two titanium screws over the right burr. The catheter (1 cm hollow fiber length) was inserted through the o-ring in the plate a depth of 3 cm. In some embodiments, the polycarbonate plate and o-ring could alternatively comprise a bioabsorable material. The catheter was primed using a Springusor™ pump to control the rate of flow during priming. The o-ring maintained the position of the catheter while it was tunneled. Both catheters were secured with stitches and the scalp sutured shut. 
     After catheters were placed, the animal was wheeled over to MRI. A baseline MRI was taken, the pig remained in a prone position during the entire imaging and infusion process. Placement of both catheters looked good. There was no backflow visible for the catheter and air bubbles and backflow were visible for the Vygon catheter. 
     The infusion was started following the baseline MRI. Both pumps were set at 3 uL/min, pressure was monitored on a catheter of this invention with a BC Biomedical™ pressure monitor. The pressure limit on the pumps was switched to the high setting. After 2 hours (360 uL), infusion was stopped and a second MRI taken. A vitamin E capsule was placed on the right side for identification purposes. For the MRI, infusion lines were disconnected at the catheter connectors (stopcocks were closed, and lines disconnected and capped). 
     Catheters were re-connected and infusion re-started until the pressure level on the Medfusion pump supplying the catheter hit it upper limit at 0.7350 ml infused (slightly over 3 hours of infusion time). The lines again were disconnected and a third MRI was taken. The infusate was 0.1% Magnevist™ solution. The contrast agent showed up well on the MR images. 
     The compression fitting used with the catheter in the last procedure (shown in  FIGS. 33-35 ) was replaced with a modified Vygon™ compression fitting with a smaller diameter stainless tube to fit the ID of the catheter. This worked well and was noted to be an improvement over the previous design illustrated in  FIGS. 33-35 . 
     The plate securing the catheter in place had to be modified to fit into the area on the scalp where it was to be secured to the skull. After cutting it down to size and screwing it in place it was effective in holding the catheter steady. Removing the catheter after the procedure was finished was not difficult and the catheter remained intact after removing it through the plate and out the tunneling pathway. Priming the hollow fiber catheter with the Springfusor™ pump provided improved properties as compared to manual syringe priming using a priming tube. While it took a few seconds longer to prime, it was a more simple process and the controlled flow rate provided by the pump was helpful. 
     Distribution with the catheter was good and there was no backflow into the burr hole. The Vygon™ catheter had a large volume of air infused and had backflow present and limited contrast agent distribution. 
     In conclusion, it can be seen that a catheter of the present invention was able to improve infusate distribution to the brain tissue target within close proximity of the hollow fiber membrane member without backflow.