Abstract:
A heat exchange catheter having an expandable insulating region thereon. The catheter has a heat exchange region and the insulating region disposed proximally thereto. The insulating region assumes a first size about a catheter shaft to facilitate insertion of the catheter into the body. Once the insulating region is inserted into the body, the insulating region is expanded a second size. The insulating region may be a balloon around the catheter shaft that is inflated to the second size to create a gap between the wall of the balloon and the catheter shaft. Heat flows through the catheter shaft to and from the heat exchange region, and thus heat loss or gain to and from the surrounding body is minimized in the insulating region. The exchange region may include a fluid circulation path comprised of lumens through the catheter shaft. A particularly useful application of the catheter is for regional cooling of blood flowing to a particular location, for example to the brain, or blood flowing to the heart to treat heart attack victims. The expandable insulating region is easy to insert through an incision or introducer sheath and expands to provide an efficient thermal barrier between the fluid circulating in the shaft and a surrounding body fluid or tissue.

Description:
FIELD OF THE INVENTION 
     This invention relates generally to thermal probes or catheters and more particularly to probes or catheters having a) a heat transmitting core (e.g. a core comprising a heated element, a lumen for transmission of hot or cold fluid, or a circuit for the circulation of hot or cold heat transfer fluid), and b) insulation on the portion of the catheter that is inserted to insulate the heat transmitting core from the portion of the patient&#39;s body adjacent the insulation. The invention also relates to methods of use of such probes or catheters. 
     BACKGROUND OF THE INVENTION 
     When a catheter or probe is inserted into a patient, it is generally desirable to have a catheter of the lowest possible diameter. If the probe or catheter is inserted into the body via an existing body orifice, such as the urethra or vagina, the acceptable diameter of the catheter is dictated by the diameter of the body orifice. On the other hand, if the probe or catheter is inserted into the body via a percutaneous puncture site or incision, as is the case in percutaneous vascular catheters or catheters inserted through a sheath or trocar during minimally invasive surgery, the acceptable diameter is dictated by the acceptable size of the percutaneous puncture site or incision. In such cases, a smaller puncture site or incision is generally preferable to a larger puncture site or incision. 
     In certain medical procedures, it is desirable to place a catheter into the body with a region that is at a different temperature than that of the surrounding body tissue. For example, in some medical procedures it is desirable to place a probe or catheter having a heat exchanger (e.g., a heatexchange surface or balloon) that is either hotter or colder than the surrounding blood, into a body lumen such as a blood vessel of a patient such that the heat exchanger will effect warming or cooling of either the blood flowing through the vessel or the tissues adjacent thereto such as the vessel wall. 
     Heat exchanging catheters may be used to exchange heat with the blood, for example, to remove heat from the blood to induce whole body or regional hypothermia for the purpose of treating, or minimizing the adverse effects of certain neurological diseases or disorders such as head trauma, spinal trauma and hemorrhagic or ischemic stroke. Additionally, it is sometimes desirable to induce whole body or regional hypothermia for the purpose of facilitating or minimizing adverse effects, such as neuronal damage, of certain surgical or interventional procedures such as open heart surgery, aneurysm repair surgeries, endovascular procedures, spinal surgeries, or other surgeries where blood flow to the brain, spinal cord or vital organs may be interrupted or compromised. Hypothermia has also been found to be advantageous to protect cardiac muscle tissue during and/or after myocardial ischemia and is protective of other tissues such as kidney or liver tissue. 
     Neural tissue such as the brain or spinal cord, is particularly subject to damage by vascular disease processes including, but not limited to ischemic or hemorrhagic stroke, blood deprivation for any reason including cardiac arrest, intracerebral or intracranial hemorrhage, and head trauma. In each of these instances, damage to brain tissue may occur because of brain ischemia, increased intracranial pressure, edema or other processes, often resulting in a loss of cerebral function and permanent neurological deficits. Likewise, during surgical procedures, it is often impossible to avoid disrupting the blood supply to all or part of the brain or spinal cord. This ischemia, even if very localized or very temporary, may nonetheless result in very serious and permanent injury to the patient. 
     Hypothermia applied to the neural tissue is known to be very neuroprotective. Although the exact mechanism for neuroprotection is not fully understood, lowering the brain temperature is believed to effect neuroprotection through several mechanisms including, the blunting of any elevation in the concentration of neurotransmitters (e.g., glutamate) occurring after ischemic insult, reduction of cerebral metabolic rate, reduction of intracranial pressure (ICP), moderation of intracellular calcium transport/metabolism, prevention of ischemia-induced inhibitions of intracellular protein synthesis and/or reduction of free radical formation as well as other enzymatic cascades and even genetic responses including apoptosis. Thus intentionally induced hypothermia of the neural tissue may prevent damage to brain or other neurological tissue during surgery or as a result of stroke, intracerebral hemorrhage and trauma. 
     The mammalian body generally functions most efficiently at normothermia. Therefore maintaining hypothermia in a portion of the body such as the brain or heart while maintaining the temperature of the rest of the body at normothermia may provide for protection of the target tissue, e.g. neuroprotection of the brain or protection of the myocardium from ischemic damage, while allowing the rest of the body to function at normothermia. Therefore a device that would facilitate the regional application of temperature exchange would be highly advantageous. 
     U.S. Pat. No. 5,486,208 (Ginsburg) describes an intravascular heat exchange catheter that comprises an elongate catheter shaft having a discrete heat transfer region located near its distal end. In one embodiment described in this patent, the catheter is inserted into a blood vessel of the patient and heat exchange fluid is circulated through the catheter shaft to the heat transfer region. By heating or cooling the heat transfer region, heat is transferred to or from the blood that flows through the vessel past the heat transfer region of the catheter. In this manner, the tissue perfused by the blood may be increased or decreased, as desired, including in some instances the entire body of the patient. Although the heat transfer is intended to occur at the discrete heat transfer region, the heated or cooled fluid is circulated through the catheter shaft proximal to the heat transfer region and no separate insulator is included to deter or prevent heat transfer from occurring between the proximal portion of the catheter shaft and the patient&#39;s blood. Thus, even though the intended site of the heat transfer may be at the heat transfer region of the catheter, some unintended heat transfer could occur between the proximal catheter shaft and the patient&#39;s blood, depending on the difference in temperature between the heat transfer fluid and the patients blood, as well as the construction of the proximal catheter shaft. 
     U.S. Pat. No. 5,624,392 (Saab) describes a heat transfer catheter apparatus that comprises very thin-walled, high strength thermoplastic tubular material defining a plurality of lumens. At least two of the lumens are adjacent to each other and readily inflatable under fluid pressure and readily collapsible under vacuum. Fluid connection means are provided at or proximate to the distal ends of the two adjacent lumens, to define a continuous loop fluid containment and circulation system. Heat transfer fluid from a first (inlet) lumen is passed directly to a second (outlet) lumen such that a continuous flow of heat transfer fluid through the two lumens can be established and maintained. Because no separate insulator is described as being formed on the exterior of the proximal portion of the Saab catheter, unintended temperature exchange could occur between the proximal catheter shaft and the patients blood, depending on the difference in temperature between the temperature exchange fluid and the patient&#39;s blood, as well as the construction of the proximal catheter shaft. 
     Also, for example, U.S. Pat. No. 4,941,475 (Williams, et al.) describes a catheter that is useable to perform thermodilution cardiac output measurements. The thermodilution catheter described by Williams et al. comprises an elongate catheter shaft, a heat exchange balloon located on the catheter shaft, a lumen that extends from the proximal end of the catheter shaft to the heat exchange balloon, and a thermistor or sensor located distal to the balloon. A bolus of heated or cooled fluid is injected through the lumen and into the heat exchange balloon. Heat is thus added to or removed from the blood flowing past the heat exchange balloon and the thermistor or sensor is used to determine the rate of temperature change in the flowing blood. The patient&#39;s cardiac output is then computed on the basis of the rate of temperature change of the flowing blood. Although the temperature exchange with the blood is intended to occur only at the location of the heat exchange balloon, no insulator is provided on the catheter shaft proximal to the heat exchange balloon and, thus, depending on the difference in temperature between the temperature exchange fluid and the patient&#39;s blood, as well as the construction of the proximal catheter shaft, some unintended heat exchange could occur between the proximal catheter shaft and the patient s blood or tissue. The unintended heat transfer to the blood at locations other than at the heat exchange balloon would affect the temperature of the blood in general, with possible adverse effects. In addition, maintaining the temperature of the heat exchange fluid at a maximum difference from the blood temperature is helpful in decreasing the noise to signal ratio and increasing the accuracy of the blood flow determination using this thermodilution catheter. Preventing the loss of heat to the blood would be very helpful in accomplishing this goal. 
     The desirability of providing some insulation on the exterior of the proximal shaft of a heat exchange catheter is addressed by U.S. Pat. No. 5,257,977 (Eschel), which describes a trans-urethral catheter useable to thermally treat prostate tissue. The catheter comprises an elongate catheter shaft, a discrete temperature exchange region, lumens that extend through the catheter shaft for circulating of heated fluid through the temperature exchange region and an insulator formed about the catheter shaft proximal to the temperature exchange region. The insulator comprises a multiplicity of sealed enclosures that contain trapped gas to decrease heat exchange between the heated liquid that is being circulated through the catheter shaft proximal to the heat exchange region and the surrounding wall of the urethra. However, the insulator of the Eschel catheter has a fixed diameter and results in an increase in the diameter of the proximal catheter shaft of the Eschel device. 
     Given the above-described desirability of minimizing the diameter of the insertion profile of the shaft of heat exchange catheters and probes during their insertion and advancement through blood vessels or other body lumens, but a simultaneous need for maximum thermal insulation of a heat exchange catheter or probe shaft after the catheter or probe is in place within the body of a patient, there exists a need in the art for the development of improved means for insulating portions of those heat exchange catheters or probes without requiring enlargement of the diameter of the catheter or probe during its insertion and advancement. 
     SUMMARY OF THE INVENTION 
     The present invention provides a heat exchange probe or catheter that generally comprises a) an elongate shaft having a proximal end and a distal end and a thermally-transmissive core; b) at least one heat exchange region formed on the elongate shaft, said heat exchange region having a tissue-contacting heat exchange surface through which heat may be exchanged between the thermally transmissive core and the adjacent body tissue (e.g., blood that flows past the heat exchange region); and c) an insulator disposed on the elongate shaft proximal to the heat exchange region, such insulator being initially disposed in a radially collapsed configuration and subsequently moveable to a radially expanded configuration. When in its radially expanded configuration, the insulator is effective to insulate the shaft to prevent exchange of heat between the thermally conductive core underneath the insulator and the patients blood or body tissue adjacent the exterior of the insulator. 
     In accordance with the invention, the insulator may comprise one or more inflatable balloons or bladders disposed about the elongate shaft proximal to the heat exchange region. For example, a plurality of elongate balloons may be disposed generally parallel to the elongate shaft so as to substantially surround the shaft and act to center the shaft between them when they are inflated. Alternatively, the insulated region may comprise a single large balloon that surrounds the shaft. The balloon may be provided with flexible attachments or other tethers extending between the shaft surface and the interior wall of the insulation balloon so that, when the insulating balloon is fully expanded, those attachments or tethers will hold the shaft in the approximate center of the insulating balloon. 
     Further in accordance with the invention, the insulator may comprise any suitable material, but preferably will comprise an inflatable, thin walled material that is relatively non-compliant, that is, will expand to a predictable diameter and then will not expand further, even if greater inflation pressure is applied. One such suitable material is polyethylene terepthalate (PET). Blood compatible insulation fluids, such as carbon dioxide or helium may be used to inflate the inflatable insulator, after the catheter has been inserted and advanced to its desired position within the patient&#39;s vasculature. 
     The heat exchange region of the catheter or probe may be formed on the elongate shaft. The thermally transmissive core of the elongate shaft may comprise one or more fluid circulation path(s) or lumen(s), whereby heated or cooled fluid may be passed into and/or extracted from the heat exchange region via the portion of the elongate shaft that is proximal to the heat exchange region. In embodiments where the thermally transmissive core comprises one or more fluid flow lumens, a heat exchange fluid may be circulated into or through the heat exchange region via such lumen(s). 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a cross section showing the catheter of the invention percutaneously inserted into a blood vessel. 
     FIG. 2 is a drawing of the distal portion of the catheter with a heat exchange balloon located in the left common carotid artery. 
     FIG. 3 is a longitudinal cross-sectional view of the proximal end of a catheter of the invention with the inflatable insulation region in a deflated condition. 
     FIG. 3A is a transverse cross-sectional view of a heat exchange fluid manifold of the catheter of the invention taken along line A—A in FIG.  3 . 
     FIG. 3B is a transverse cross-sectional view of the heat exchange fluid manifold taken along line B—B in FIG.  3 . 
     FIG. 3C is a transverse cross-sectional view of an insulation fluid manifold of the catheter of the invention taken along line C—C in FIG.  3 . 
     FIG. 3D is a transverse cross-sectional view of an inflatable insulation region of the catheter of the invention, shown uninflated, and taken along line D—D in FIG.  3 . 
     FIG. 4 is a longitudinal cross-sectional view of the proximal end of the catheter of the invention with the inflatable insulation region in an inflated condition. 
     FIG. 4A is a transverse cross-sectional view of the inflatable insulation region of the catheter of the invention, shown inflated, and taken along line A—A in FIG.  4 . 
     FIG.  4 A′ is a transverse cross-sectional view of an alternative embodiment of the inflatable region of the catheter of the invention, shown inflated, and again taken along line A—A in FIG.  4 . 
     FIG. 5 is an elevational view of a heat exchange region of a catheter of the invention. 
     FIG. 5A is an elevational view of an alternative heat exchange region of the present invention. 
     FIG. 6 is an elevational view of a shaft portion of the catheter with the twisted heat exchange balloon seen in FIG. 5 removed. 
     FIG. 7 is an isolated view of the twisted heat exchange balloon of the catheter depicted in FIG.  5 . 
     FIG. 8 is a detailed view of a proximal section of the heat exchange region of the catheter taken within the circle  8  in FIG.  5 . 
     FIG. 9 is a detailed view of a distal section of the heat exchange region of the catheter taken within the circle  9  in FIG.  5 . 
     FIG. 10 is transverse cross-sectional view of the shaft of the catheter taken along line  10 — 10  in FIG.  6 . 
     FIG. 11 is a transverse cross-sectional view of the twisted heat exchange balloon taken along line  11 — 11  in FIG.  7 . 
     FIG. 12 is a transverse cross-sectional view of a proximal section of the heat exchange region of the catheter taken along line  12 — 12  in FIG.  5 . 
     FIGS. 12A-12 c  are transverse cross-sectional views of the alternative heat exchange region of the catheter of FIG.  5 A. 
     FIG. 13 is a transverse cross-sectional view of a mid-section of the heat exchange region of the catheter taken along line  13 — 13  of FIG.  5 . 
     FIG. 14 is a transverse cross-sectional view of a distal section of the heat exchange region of the catheter taken along line  14 — 14  of FIG.  5 . 
     FIG. 15 is a schematic elevational view of a heat exchange catheter of the present invention inserted femorally and through the abdominal aorta of a patient so that a heat exchange region is located in one of the carotid arteries. 
     FIG. 15A is a detailed view of a heat exchange region of the catheter of FIG. 15 taken within the circle  15 A. 
     FIG. 16 is a plan view of a segment of the heat exchange region of the catheter of FIG.  15 . 
     FIG. 16A is a cross-sectional view of the heat exchange region of FIG. 16, taken along line  16 A— 16 A. 
     FIG. 17 is a longitudinal cross-sectional view of a proximal manifold portion of the heat exchange region of the catheter of FIG.  15 . 
     FIG. 17A is a transverse cross-sectional view of the heat exchange region taken along line  17 A— 17 A of FIG.  17 . 
     FIG. 17B is a transverse cross-sectional view of the heat exchange region taken along line  17 B— 17 B of FIG.  17 . 
     FIG. 17C is a transverse cross-sectional view of the heat exchange region taken along line  17 C— 17 C of FIG.  17 . 
     FIG. 18 is a longitudinal cross-sectional view of a proximal manifold portion of the heat exchange region of the catheter of FIG.  15 . 
     FIG. 18A is a transverse cross-sectional view of the heat exchange region taken along line  18 A— 18 A of FIG.  18 . 
     FIG. 18B is a transverse cross-sectional view of the heat exchange region taken along line  18 B— 18 B of FIG.  18 . 
     FIG. 19 is a schematic elevational view of an alternative heat exchange region suitable for use with the heat exchange catheters of the present invention. 
     FIG. 20 is a schematic elevational view of another alternative heat exchange region suitable for use with the heat exchange catheters of the present invention. 
    
    
     DETAILED DESCRIPTION 
     The present invention provides a heat exchange catheter with an improved insulation region on the shaft of the catheter, which insulation region provides improved thermal insulation without significantly increasing the insertion profile of the catheter. Although the present invention is primarily intended to be used in the bloodstream with a catheter that cools blood flowing to specific locations in the patient&#39;s body to regulate the temperature of tissue at that location, those of skill in the art will readily appreciate that various other applications for the insulation region of the present invention are possible. Indeed, the present invention may have applications beyond controlling the temperature of tissue and circulating body fluid, and the claims should not be so limited. 
     In a preferred application, a catheter of the present invention is positioned within a patient&#39;s vasculature to exchange heat with the blood in order to regulate the overall body temperature, or to regulate the temperature of a localized region of the patient&#39;s body. The catheter of the present invention may be, for example, suitable for exchanging heat with arterial blood flowing toward the brain to cool the brain, and may thus prevent damage to brain tissue that might otherwise result from a stroke or other injury. Or the catheter may be used to cool venous blood flowing toward the heart to cool the myocardium and prevent tissue injury that might otherwise occur following a myocardial infarct (MI) or other similar event. 
     Referring now to FIGS. 1 and 2, an exemplary embodiment of the heat exchange catheter  10  of the invention comprises a proximal hub  12 , a shaft  14 , an insulating sheath  16 , a heat exchange region  18  which may be in the form of an inflatable balloon, and a distal tip  29 . The hub  12  may include a working port  22 , an inflow port  24 , an outflow port  26 , and an inflation port  28 . 
     As seen in FIG. 3, a length of the proximal end of the catheter shaft  14  is contained within the hub  12 . The hub  12  may be sealed around the shaft  14 , such as by injection molding, or the shaft may be inserted into a bore formed through the hub. For example, the hub may be separately formed with a throughbore into which the shaft  14  inserts and is affixed with, for example, adhesives or thermal bonding. With reference to FIGS. 3A and 3B, the shaft  14  has three lumens running along its length to the distal tip  29 : a working lumen  30 , an inflow lumen  32  and an outflow lumen  34 . The working port  22  communicates with the working lumen  30  so that the operator may insert items through the working port, through the working lumen and thus out the distal tip  29  of the catheter. For example, a guide wire  36  may be inserted into the working lumen  30  and out the distal tip  29  to guide the insertion of the catheter. Likewise, the working lumen  30  may be useful for injection of medicaments, insertion of a temperature probe, measurement of pressure, and the like. 
     For purposes of this description the inflow lumen is lumen  32 , and the outflow lumen is  34 . As one of skill in the art may readily appreciate, the direction of flow of the heat exchange fluid, as described below, may be reversed if desired by reversing the flow in the inflow and outflow lumens. 
     As seen in FIG. 2, the heat exchange catheter  10  of this embodiment has a heat exchange region  18 , preferably in the form of a balloon, that receives heat exchange fluid from the inflow lumen  32  of the shaft  14 . The heat exchange fluid circulates through the balloon interior and returns proximally along the shaft  14  through the outflow lumen  34 . The heat exchange region  18 , in conjunction with a shaft  14  of the configuration of the embodiment described herein, is illustrated in greater detail in FIGS. 5 through 14. 
     An inflow channel  42  is formed through the inflow port  24  and hub  12 , and an opening  38  (FIG. 3A) is formed in the wall of the inflow lumen in the portion of the shaft  14  contained within the hub. The inflow channel  42  is in fluid communication with inflow lumen  32  at the opening  38 . Similarly, an outflow channel  44  is formed through the outflow port  26  and hub  12 , and an opening  40  (FIG. 3B) is formed in the wall of the outflow lumen  34  in the portion of the shaft  14  contained within the hub. The outflow channel  44  is in fluid communication with the outflow lumen  34  at the opening  40 . As seen in FIGS. 3 and 4, an inflation manifold  46  is located around the catheter shaft  14  distally with respect to the hub  12 . An inflation channel  48  extends through the inflation port  28 , and communicates with an interior space  50  of the inflation manifold  46 . As seen in FIGS. 3 and 3C, a seal  52  is formed, for example by adhesive or potting compound, between the inflation manifold  46  and a coupling end  54  provided on the proximal end of the insulating sheath  16 . The interior volume of the insulating sheath  16  is in fluid communication with the interior space  50  of the inflation manifold  46  so that an inflation medium such as CO 2  or Helium may be introduced through the inflation port  28  via the inflation channel  48  to inflate the insulating sheath. Consequently, the insulating sheath  16  may be expanded from an uninflated state (e.g., as seen at  16  in FIG. 3) by the introduction of an inflation medium, to an inflated state, as seen at  16  in FIG.  4 . 
     In some embodiments, various means may be provided to center the insulated portion of the shaft within the insulation sheath. As seen in FIGS. 3D and 4A, tethers  56  may be provided to attach the inner surface of the insulation sheath  16  to the outer surface of the shaft  14 . When the insulation sheath  16  is fully inflated, these tethers  56  serve to generally center the shaft  14  within the insulating sheath. The centering function of the tethers  56  serves to maximize the overall insulating effect of the inflated sheath  16  by keeping the shaft  14  as far away from the walls of the sheath as possible, thus ensuring that the shaft will have the maximum insulated distance at all points along its length. For example, when the insulated shaft  14  is located in a blood vessel with flowing blood, the outside of the insulating sheath  16  is in thermal contact with the blood, and a uniform insulating gap is provided concentrically surrounding the shaft  14 . Altematively, the centering elements  56  may be collapsible stand-offs attached to the outer surface of the shaft  14  to hold the inflated sheath  16  away from the shaft and thereby center the shaft within the insulating sheath. 
     Another method of centering the shaft  14  within the insulating sheath employs a structure with multiple thin-walled tubes surrounded by the sheath  16 , said tubes readily inflatable under pressure and collapsible under vacuum. This construction is depicted in FIG.  4 A′. A central thin-walled tube  58  large enough to accommodate the shaft  14  is surrounded by a plurality of internal tubes  60 ,  61 ,  62 ,  63 . When all the lumens defined by the internal tubes  60 ,  61 ,  62 ,  63  are inflated, they hold the insulating sheath  16  around the shaft  14  at a uniform distance approximately equal to the diameter of the internal lumens. In this way the shaft  14  is centered within the insulating sheath. 
     Any number of heat exchange probes or catheters may utilize the expandable insulation of this invention. One example of a catheter for such use is shown and described in relation to FIGS. 5 through 14 inclusive. 
     As seen in FIGS. 5 and 7, the assembled catheter  10  has an exemplary heat exchange region  18  in the form of a four-lumen, thin-walled balloon  70  which is attached over the distal portion of the catheter shaft  14 . The cross-sectional view of the four-lumen balloon  70  is shown in FIG.  11 . The balloon has three elongated lobes that define outer lumens  74 ,  76 ,  78  and are wound in a helical pattern around an inner lobe defining an inner lumen  80 . All four lumens are defined by the lobes of a thin walled balloon (and can be viewed as four separate balloons), and each outer lumen  74 ,  76 ,  78  shares a common thin wall segment  82  with the inner lumen  80 . When installed, both the proximal end  84  and the distal end  86  of the balloon  70  are sealed around the shaft in a fluid tight seal. 
     Over the proximal length of the catheter, between the hub  12  and the proximal balloon attachment  84 , the shaft  14  is at the extruded outer diameter of about 0.118 inches. The internal configuration is as shown for example, in cross-section  3 D or in the shaft as shown in FIG.  4 A. Immediately proximal of the balloon attachment  84 , the shaft  14  is necked down at  88 . The outer diameter of the shaft  14  is reduced to about 0.10 to 0.11 inches, but the internal configuration of the lumens is maintained. Compare, for example, the shaft cross-section of FIG. 10 with the cross-section shown in FIG.  12 . This length of reduced diameter shaft  14  remains at approximately constant diameter of about 0.10 to 0.11 inches between the necked down location at  88  and a further necked down location at  90  (FIG.  6 ). 
     On the necked down location  88 , a proximal balloon marker band  91  is attached around the shaft  14 . The marker band is a radiopaque material such as a platinum or gold band or radiopaque paint, and is useful for locating the proximal end of the balloon  70  by means of fluoroscopy while the catheter is within the body of the patient. 
     At the marker band  91 , all four lobes of the balloon  70  are reduced down and are fastened to the inner member at  84  (see FIG.  5 ). This may be accomplished by folding the balloon  70  down around the shaft  14 , placing a sleeve, for example a short length of tubing, over the balloon and inserting adhesive, for example by wicking the adhesive, around the entire inner circumference of the sleeve. This simultaneously fastens the balloon  70  down around the shaft  14 , and creates a fluid tight seal at the proximal end of the balloon. 
     Distal of this seal, under the balloon  70 , a series of axially-spaced windows  92 ,  94 ,  96  is cut through the wall of the outflow lumen  34  in the shaft  14 , as seen in FIG.  6 . Juxtaposed to these windows, groups of slits  98 ,  100 ,  102  are cut into the wall of the outer balloon lumens  74 ,  76 ,  78 , respectively. Because the outer tubes having the outer lumens  74 ,  76 ,  78  are twined about the shaft  14  in a helical fashion, each of the outer lumens passes over a generatrix of the shaft adjacent the outflow lumen  34  of the shaft at a slightly different axial location. Therefore, where each outer lumen  74 ,  76 ,  78  passes over the outflow lumen  34 , one of the windows  92 ,  94 ,  96  is registered with one of the groups of slits  98 , 100 ,  102  to fluidly connect the proximal portion of the respective outer lumens  74 ,  76 ,  78  to the outflow lumen of the shaft  14 . 
     Alternatively, as shown in FIGS.  5 A and  12 A- 12 C, an elongate window  92 ′ may be cut through the wall of the outflow lumen  34 ′. As shown in FIGS. 12A-12C an annular space  91 ′ surrounds the shaft  14 ′ within the inner lobe of the balloon  70 ′ that forms the inner lumen  80 ′. Along the portion of the balloon over the proximal shaft that includes the elongate window  92 ′, five groups of slits  98 ′,  100 ′ and  102 ′ are cut into the common wall between each of the outer balloon lumens and the inner lumen  80 ′. Because the outer lumens  74 ′,  76 ′,  78 ′ are twined about the inner lumen  80 ′ in a helical fashion, each of the outer tubes passes over the outflow lumen of the inner shaft member at a slightly different location along the length of the inner shaft. The elongate window  92 ′ is sufficiently long that each of the outer lumens passes  74 ′,  76 ′,  78 ′ over the elongate window at a point where at least one slit from each group of the slits  98 ′,  100 ′ and  102 ′ is cut into the common wall (as depicted in the cross-sections  12 A- 12 C). The other slits open into the space  91 ′ which, in turn, is in fluid communication with the outflow lumen  34 ′. In this way each of the outer lumens  74 ′,  76 ′,  78 ′ is in fluid connection with the outflow lumen  34 ′ over a relatively short distances of the balloon, either directly through a slit over the elongate window  92 ′, or via the annular space  91 ′. FIG. 5A shows the slits in all the exterior balloon lobes as being formed along the same linear axis over the window  92 ′, but it will be readily perceived that the windows may be staggered around the balloon so that they are formed along a shorter length of the balloon, for example 2 cm. Desirably, because of the length of the window  92 ′ and the pitch of the twisted lobes, at least one of the slits in each group will be positioned directly over the window. 
     Distal of the windows  92 ,  94 ,  96  in the outflow lumen  34 , the tube defining the inner lumen  80  of the four-lumen balloon  70  is sealed around the shaft  14  in a fluid tight seal, as indicated in FIG. 5 at  104 . The outflow lumen  34  is thereafter plugged as seen at  106 , and the inflow lumen is open to the inner lumen  80 . (See FIG. 13.) As shown in FIG. 13, this may be accomplished by necking down the shaft  14  to seal the outflow lumen shut at  106 , removing the wall of the inflow lumen  32 , piercing a small hole in the wall of the inner lumen at  110 , wicking UV curable adhesive into the hole and around the entire outside of the shaft, and then curing the adhesive to create a plug  111  about the wall of the shaft  14 . This adhesive plug serves to prevent the portion of the inner lumen proximal to the plug  111  from being in fluid communication with the inner member distal to the plug. 
     With reference to FIG. 6, the guide wire lumen  30  of the shaft may be terminated and joined to a guide wire tube  112  at a location just distal of the necked down location  90 . The distal end  86  of the balloon  70  including all four lumens of the balloon is sealed down around the guide wire tube  112  in a manner similar to the way the balloon is sealed at the proximal end  84  around the shaft  14 . This seals all four lumens of the balloon  70  in a fluid tight seal. Just proximal of the seal, slits  116  (FIGS. 5 and 7) are cut into the common wall between each of the three outer lumens  74 ,  76 ,  78  of the balloon  70  and the inner lumen  80  so that each of the outer lumens is in fluid communication with the inner lumen. (See FIG.  9  and FIG. 14.) In this way, the inflow lumen  32  is open into the inner lumen of the four-lobed balloon  70  and the inner lumen in turn is in fluid communication with the distal ends of each of the three outer lobes. 
     Just distal of the balloon  70 , near the distal seal, a distal marker band  118  is placed around the guide wire tube  112 . A flexible length of tube  120  may be joined onto the distal end of the guide wire tube  112  to provide a flexible tip to the catheter  10 . The distal end  29  of the flexible tube  120  is open so that a guide wire may exit the tip, or medicine or radiographic fluid may be injected distal of the catheter through the working lumen. 
     In use, the catheter  10  is inserted into the patient, for example, percutaneously into a blood vessel BV by the well known Seldinger technique. The catheter  10  may be directly inserted, or may be inserted through an introducer sheath  64  (FIG.  1 ). In order to minimize the diameter of the catheter, the catheter is inserted with the insulating sheath  16  in an uninflated condition (FIG.  3 ). When the catheter is in place, the insulating sheath  16  may be inflated (FIG. 4) with a suitable inflation fluid, for example with a biocompatible gas such as CO 2  or Helium. A suitable inflation medium will be any fluid that is provides adequate insulation, is non-toxic, and generally will dissolve in blood so that, should a leak occur in the insulating balloon, the escaping gas will dissolve in the blood and be expelled through the lungs and will not form harmful bubbles in the blood stream. 
     The gap formed between the insulating sheath  16  and the shaft  14  provides excellent thermal insulation, and the tethers  56  (FIG. 4A) or tubes  60 ,  61 ,  62 ,  63  (FIG.  4 A′) center the shaft within the inflated insulated region. Preferably, the inflation fluid will be maintained within the insulating sheath  16  at relatively low pressures. The portion of the insulating sheath  16  that is within the introducer sheath  62  or the incision will not fully inflate at the relatively low pressures that are used, though the inflation medium will be permitted to pass through such narrowed regions. The inflation pressure should be sufficient to fully inflate the portion of the insulating sheath that is within the blood vessel against normal blood pressures, and sufficient pressure to flow through the sheath or incision to inflate the sheath, but no greater so that if there is a rupture, only a minimal amount of inflation medium will be introduced into the blood stream. In an exemplary embodiment, the inflation pressure should be no more than 2 psi above blood pressure in the vessel in which it is located. Additionally, the inflation source desirably has a flow restrictor that limits inflow of inert gas to the interior of the insulation region to a rate similar to the rate the gas would be absorbed by the body, e.g., 2 cc/min to 3 cc/min if the inflation medium is CO 2 . 
     The catheter is inserted into the body of a patient so that the balloon  70  is within a blood vessel BV. Heat exchange fluid is circulated into the inflow port  24 , travels down the inflow lumen  32  and into the inner lumen  80  of the four-lumen balloon  70 . The heat exchange fluid travels to the distal end of the inner lumen  80  and then through the slits  116  between the inner lumen  80  and the outer lumens  74 , 76 , 78 , as depicted in FIG.  9 . 
     The heat exchange fluid then travels back through the three outer lumens  74 ,  76 ,  78  of the balloon  70  to the proximal end of the balloon in a helical flow pattern. At some point along the proximal portion of the shaft, each outer lumen is located over the portion of the shaft having a window  92 ,  94 ,  96  to the outflow lumen  34  and the outer balloon lumens have slits  98 ,  100 ,  102  that are aligned with the windows. The heat transfer fluid passes through the slits  98 ,  100 ,  102  through the windows  92 ,  94 ,  96  and into the outflow lumen  34 . For instance, FIG. 8 shows fluid passing from the lumens  74 ,  76 ,  78  through slits  102  and window  96  into outflow lumen  34 . From there it is circulated out of the catheter through the outflow port  26 . 
     Counter-current circulation between the blood and the heat exchange fluid is highly desirable for efficient heat exchange between the blood and the heat exchange fluid. Thus if the balloon is positioned in a vessel where the blood flow is in the direction from proximal toward the distal end of the catheter, for example if it were placed from the femoral artery, through the aorta and then into the left common carotid, the blood flow in the left common carotid would be flowing past the heat exchange region of the catheter in a direction from the proximal to the distal part of the heat exchange region. It would be most efficient in this situation to have the heat exchange fluid in the outer balloon lumens flowing from the distal end toward the proximal end, as described above and shown in the figures. It is to be readily appreciated, however, that if the balloon were placed so that the blood was flowing along the catheter in the direction from distal to proximal, such as, for example, if the heat exchange region was placed into the inferior vena cava with a jugular insertion, it would be desirable to have the heat exchange fluid circulate in the outer balloon lumens from the proximal end to the distal end. This could be accomplished by merely reversing which port is used for the inflow direction and which for the outflow. 
     Where it is important that the heat exchange medium, for example heat exchange fluid, be carried to the heat exchange region with as little heat exchange along the way as possible, thermal insulation along that length of the catheter shaft is particularly helpful. This may be true if a regional heating or cooling effect is desired, as would be the case with regional cooling of the brain as described below, or if the tissue between the insertion point and the heat exchange region needed to be protected from temperature exchange with the shaft. An example of the lafter situation is where very hot fluid is transmitted to the heat exchange region, as might be the case with heated balloon angioplasty, a thermodilution procedure, or thermal ablation at the heat exchange region. In such situations, an inflatable insulation region along the catheter length would be particularly desirable. 
     In particular, the heat exchange catheter  10  of the present invention is useable to perform regional percutaneous temperature regulation (rPTR™) (the acronym rPTR is a trademark of Radiant Medical, Inc. of Redwwod City, Calif.). Such rPTR™ procedure is accomplished by percutaneously inserting the catheter  10  into a blood vessel and advancing the catheter  10  through the patient&#39;s vasculature until its heat exchange region  18  is positioned within or slightly upstream of the particular region of the body that is to be heated or cooled. A heated or cooled heat exchange medium is infused through the catheter shaft  14  to the heat exchange region  18 . During such infusion of the heat exchange medium, insulating sheath  16  is deployed or utilized to minimize heat exchange between the catheter shaft  14  proximal to the heat exchange region  18  and the patient&#39;s blood flowing thereby. In this manner, effectve heat exchange with the patient&#39;s blood occurs only at the heat exchange region  18  of the catheter  10 . 
     Such devices where the inflatable insulating sheath of this invention would be particularly advantageous would be, for example, in heat exchange catheters intended to provide directed cooling to a patient&#39;s brain. Such a catheter might be constructed as shown in FIGS. 15-20. Other catheters where the inflatable insulating sheath of this invention would be particularly advantageous are disclosed in U.S. Pat. No. 5,957,963 to Dobak, III, and in WO 99/48449, both assigned to Del Mar Medical Technologies, Inc. 
     The magnitude of heat exchange is a function of the difference between the temperature of the blood flowing past the heat exchange region and the temperature of the surface of the heat exchange elements, a difference that may be described as ΔT. If cooled (or heated) blood is to be directed to a specific location in the patient, the greatest ΔT must be maintained between the heat transfer region and the blood that subsequently flows to that region. 
     In the case of directing the cooled blood to the patient&#39;s brain, the heat transfer catheter may be inserted into the leg or abdominal region and advanced through the vasculature, forexample up the aorta  124 , to the carotid artery  126 . This general configuration is shown if FIG.  2 . The heat transfer region  18  is placed essentially entirely into the carotid artery. Heat transfer fluid is circulated from outside the patient, up the shaft  14 , to the heat transfer region  18 , and then back down the shaft and out of the body. The desired effect is to cool blood directed through the carotid to the brain and thus cool the brain. All heat transferred to the heat exchange medium in the shaft  14  from the blood in the aorta  124  would affect primarily blood being carried away from the head and would not serve to cool the brain. In fact, where the operator desires to maintain normothermia in the rest of the body while cooling only the brain, this lost heat would serve to undesirably cool the rest of the body. Not only would the heat transferred in the aorta serve to cool the rest of the body and not the brain, but it would simultaneously decrease the cooling effect directed to the brain by increasing the temperature of the heat exchange fluid and thus decreasing the ΔT between the heat exchange region and the blood of the patient. 
     An effective insulating member along the catheter shaft may prevent undue thermal exchange between the heat exchange fluid proximal ofthe heat exchange region, and thus ensure the maximum ΔT between the heat exchange region and the patient&#39;s blood. However, most truly effective thermal insulation available prior to the invention are sufficiently bulky to unacceptably increase the diameter of the catheter assembly prior to insertion so that percutaneous insertion into a small incision or through a small conduit such as a sheath trocar or body orifice, is not feasible. In contrast, the inflatable insulation of the invention could be inserted in its uninflated state into a body cavity such as a blood vessel, the peritoneal cavity, the bladder or the like through an incision or conduit that is significantly smaller in diameter than the cavity, inflated after insertion, and provide effective insulation. In this way, maximum temperature differential between the heat exchange region and the target tissue may be maintained while avoiding unwanted heat exchange between the shaft and the tissue that may be in contact with the shaft region. Desirably, the insertion channel, be it formed by a percutaneous incision or puncture or by a trocar or introducer, for example, is preferably 9 French or less in size, but may be larger, for example as large as 13 French. 
     FIGS. 15-20 illustrate various heat exchange regions suitable for use with catheters of the present invention. In particular, the heat exchange regions shown can be provided on the distal portion of a heat exchange catheter, wherein an insulating region is provided on a proximal portion, or along the entire proximal length of the catheter that is within the body. 
     For example, FIGS. 15 and 15A illustrate a heat exchange catheter  200  inserted through one of the femoral arteries and advanced until a heat exchange region  202  is located within one of the carotid arteries of the neck. The catheter  200  comprises the heat exchange region  202  on a distal end, an elongate insulating region  204  located proximally thereto, and an inner shaft  206  extending substantially the entire length of the catheter. The catheter  200  passes into the body through an introducer  208  and includes a proximal hub  210 . The heat exchange region  202  is connected to the shaft  206 , as best  20  seen in FIG.  15 A. Heat is transferred to and from the heat exchange region  202  via the shaft  206 , and the insulating region  204  helps improve the efficiency of the device by inhibiting heat transfer between the vasculature and the shaft  206 . 
     In a preferred embodiment, heattransferfluid circulates to and from the heat exchange region  202  via channels formed in the shaft  206 . FIGS. 16 and 16A illustrate one exemplary embodiment of a heat exchange region  202  comprising a plurality of tubular members that are stacked in a helical plane. More specifically, a central tube  220  defines a central lumen  222  therewithin. A pair of smaller intermediate tubes  224   a ,  224   b  attaches to the exterior of the central tube  220  at diametrically opposed locations. Each of the smaller tubes  224   a ,  224   b  defines a fluid lumen  226   a ,  226   b  therewithin. A pair of outer tubes  228   a ,  228   b  attaches to the exterior of the intermediate tubes  224   a ,  224   b  in alignment with the aligned axes of the central tube  220  and intermediate tubes  224   a ,  224   b . Each of the outer tubes  228   a ,  228   b  defines a fluid lumen  230   a ,  230   b  within. By twisting the intermediate and outer tubes  224   a ,  224   b ,  228   a ,  228   b  around the central tube  220 , the helical ribbon-like configuration of FIG. 16 is formed. 
     An inflow path of heat exchange medium is provided by the central tube  220 , as described in greater detail below. The intermediate tubes  224   a ,  224   b  and outer tubes  228   a ,  228   b  define a fluid outflow path within the heat exchange region  202 . Heat exchange fluid is transferred into the catheter  200  through an inflow port  240  of the hub  210 , as seen FIG. 15, and is removed from the catheter  200  through an outflow port  242 . A working lumen port  244  is also provided on the hub  210 . 
     Now with reference to FIGS.  17  and  17 A- 17 C, a proximal manifold of the heat exchange region  202  will be described. The shaft  206  extends a short distance, desirably about 3 cm, within the central tube  220  and is thermally or adhesively sealed to the interior wall of the central tube as seen at  250 . As seen in FIG. 17A, the shaft  206  includes a planar bulkhead  252  that generally evenly divides the interior space of the shaft  206  into an inflow lumen  254  and an outflow lumen  256 . A working or guidewire lumen  260  is defined within a guidewire tube  262  that is located on one side of the shaft  206  in line with the bulkhead  252 . Desirably, the shaft  206  is formed by extrusion. The outflow lumen  256  is sealed by a plug  264  or other similar expedient at the terminal end of the shaft  206 . The inflow lumen  254  remains open to the central lumen  222  of heat exchange region  202 . The guidewire tube  262  continues a short distance and is heat bonded at  270  to a guidewire extension tube  272  generally centered within the central tube  220 . 
     A fluid circulation path is illustrated by arrows in FIG.  17  and generally comprises fluid passing distally through the inflow lumen  254  and then through the entirety of the central lumen  222 . Fluid returns through the lumens  226   a ,  226   b , and  230   a ,  230   b  of the intermediate and outer tubes  224   a ,  224   b , and  228   a ,  228   b , respectively, and enters reservoirs  274  and  275 . Alternatively, two windows may be formed  276  and a counterpart not shown in FIG. 17 one helical twist farther down the shaft, between each side of the twisted ribbon (i.e., lumens  224   a  and  224   b  on one side, and  228   a  and  228   b  on the other side). in this way, one reservoirfrom each side of the twisted ribbon is formed in fluid communication with the outflow lumen  256  (configuration not shown). Fluid then enters the outflow lumen  256  through apertures, e.g.,  276 , provided in the central tube  206  and a longitudinal port  278  formed in the wall of the shaft. 
     A distal manifold of the heat exchange region  202  is shown and described with respect to FIGS.  18  and  18 A- 18 B. The outer tubes  228   a ,  228   b  taper down to meet and seal against the central tube  220  which, in turn, tapers down and seals against the guidewire extension tube  272 . Fluid flowing distally through the central lumen  222  passes radially outward through a plurality of apertures  280  provided in the central tube  220 . The apertures  280  open to a distal reservoir  282  in fluid communication with lumens  226   a ,  226   b , and a distal reservoir  281  in fluid communication with lumens  230   a ,  230   b  of the intermediate and outer tubes  224   a ,  224   b , and  228   a ,  228   b.    
     With this construction, heat exchange fluid introduced into the input port  240  will circulates through the inflow lumen  254 , into the central lumen  222 , out through the apertures  280 , and into the distal reservoir  282 . From there, the heat exchange fluid will travel proximally through both intermediate lumens  226   a ,  226   b  and outer lumens  230   a ,  230   b  to the proximal reservoirs  274  and  275 . Fluid then passes radially inwardly through the apertures  276  and port  278  into the outflow lumen  256 . Then the fluid circulates back down the shaft  206  and out the outlet port  242 . 
     The twisted ribbon configuration of FIGS. 15-18 is advantageous for several reasons. First, the relatively flat ribbon does not take up a significant cross-sectional area of a vessel into which it is inserted. The twisted configuration further prevents blockage of flow through the vessel when the heat exchange region  202  is in place. The helical configuration of the tubes  224   a ,  224   b ,  228   a ,  228   b  also aids to center the heat exchange region  202  within a vessel by preventing the heat exchange region from lying flat against the wall of the vessel along any significant length of the vessel. This maximizes heat exchange between the lumens and the blood flowing next to the tubes. Because of these features, the twisted ribbon configuration is ideal for maximum heat exchange and blood flow in a relatively small vessel such as the carotid artery. As seen in FIG. 16A, an exemplary cross-section has a maximum diameter of about 5.9 mm, permitting treatment of relatively small vessels. 
     In any configuration, for maximum heat exchange results, it is important that the difference in temperature between the blood and heat exchange region be as large as possible. Because of the long length of catheter required for selective cooling of the brain within the carotid artery in conjunction with femoral insertion, maximum thermal insulation of the shaft is important to maximize heat transfer with the blood flowing to the brain and minimize heat transfer with the blood flowing away from the brain. Because the catheter is passed through the abdominal aorta, which is relatively large, there is room within this artery to utilize an inflatable insulating region  204  as previously described. Because the insulating region  204  is first deflated, the incision or puncture into the arterial system is minimized. 
     Other heat exchange regions suitable for use with catheters of present invention are seen in FIGS. 19 and 20. In FIG. 19, a flexible metal heat exchange region  300  comprises a bellows configuration with a convoluted surface having heat exchange fins in the shape of annular folds. The annular folds are desirably hollow and receive circulating heat exchange fluid within. Again, the effectiveness of the heat exchange region  300  is enhanced with the use of an insulating region  302  surrounding the catheter shaft. In FIG. 20, a flexible metal heat exchange region  310  comprises a hollow metal element having spiral heat exchange fins on the external surface. A co-axial central tube (not shown) delivers heat exchange fluid into an inner space of the heat exchange region  310 . Again, an insulating member  312  surrounds the shaft of the exchange catheter for maximum efficiency. 
     While a particular embodiment of the invention has been described above, for purposes of illustration, it will be evident to those skilled in the art that numerous variations of the details may be made without departing from the invention as defined in the appended claims. By way of example and not limitation, the heat transfer fluid could be a liquid or a gas, the heat transfer region could be in the forrn of a balloon, a flexible metallic member, a region with multiple discrete heat exchange members or the like, all without deviating from the spirit of this invention. Similarly othervariations of the embodiments described are anticipated within the scope of the invention as claimed.