Abstract:
The invention provides a method and apparatus for performing selective hypothermia to the brain and spinal cord for injury protection without the need for systemic cooling. A flexible catheter is inserted into the cerebral lateral ventricle or spinal subdural space. The catheter has lumens with a heat transfer element. The lumens of the catheter circulate a coolant and communicate at the distal heat transfer element for transfer of heat from the cerebrospinal fluid. Furthermore a method of maintaining catheter patency and providing blood clot hemolysis and drainage is also provided through the use of ultrasonic and/or laser energy delivered through the catheter.

Description:
[0001]     This application is a continuation of U.S. application Ser. No. 10/136,003 filed Dec. 20, 2002, titled “Selective brain and spinal cord hypothermia method and apparatus,” now U.S. Pat. No. 6,699,269.  
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     The current invention relates to regulation of the temperature in the brain and spinal cord. The invention describes a method and apparatus for altering the temperature of the brain surface and/or the cerebrospinal fluid in the ventricles of the brain and surrounding the spinal cord.  
         [0003]     Hypothermia has been shown to provide cerebral and spinal cord injury protection from either trauma, ischemia, or hypoxia. Ischemia may occur from cardiac arrest, cardiac failure, stroke, head or spinal cord injury, aneurysm surgery, cardiac surgery, and aortic or carotid surgery. Hypothermia is also effective in reducing increased intracranial pressure from cerebral swelling. The mechanisms involved in hypothermic cerebral protection are several-fold and include 1) reduction in cerebral glucose and oxygen metabolism and decreasing lactate content following injury, 2) preventing disruption of the blood brain barrier and consequently reducing cerebral edema, 3) reduction of endogenously toxic neurotransmitters like glutamate, glycine, aspartate, acetylcholine, and norepinephrine into the brain after injury, 4) inhibit excessive calcium entry and intracellular calcium overload into neurons, 5) protecting membrane structural proteins like microtubule-associated protein-2, and 6) preventing diffuse axonal injury following brain trauma.  
         [0004]     In general, the human brain and spinal cord are maintained at a constant temperature of approximately 37 to 38 degrees celsius. Hypothermia is considered mild when the body temperature is 33 to 35 degrees celsius, moderate between the temperatures of 28 to 32 degrees, and severe in the temperature range of 24 to 28 degrees celsius. Most studies in humans have involved mild to moderate systemic hypothermia mainly because of the significant side effects that occur from induced systemic hypothermia. These include infection, cardiac arrhythmias, coagulopathy, renal failure, as well as rewarming shock. In order to avoid these complications the degree and duration of hypothermia has been shortened thereby limiting its effectiveness.  
         [0005]     Generally, cooling of the brain has been accomplished through whole body cooling with use of a cooling blanket, immersing the patient in ice, or cooling the blood through a cardiopulmonary bypass machine. A few methods have been described regarding selective brain and spinal cord hypothermia. These involve cooling the arterial vessel or blood supply to the brain or external cooling helmets, each with its own significant limitations.  
         [0006]     Several catheters have been developed to induce systemic hypothermia by inserting them into the bloodstream. More recently catheters have been developed that can be inserted into the arterial vessels to the brain to induce selective brain hypothermia. These catheters are limited in their size and finctionality by the small vessel lumen as well the inability to cool all the four major arterial vessels supplying blood to the brain and are unable to cool the spinal cord via this methodology. They also carry the risk of ischemic and thromboembolic stroke by either impairing the blood flow to the brain or dislodging clots that can develop in intra-arterial catheters.  
         [0007]     External cooling helmets have limited effectiveness since the blood to the cooled scalp does not circulate into the brain and returns systemically which along with the thick skull dilutes the hypothermic effect to the brain.  
         [0008]     Selective brain and spinal cord cooling with insertion of catheters into the ventricular, subdural or epidural space as described in U.S. Pat. No. 6,699,269 to Khanna is a novel concept. It also describes a catheter that expands with circulation of a coolant without direct contact of the coolant with the central nervous system. This avoids the side effects and complications seen from other methods of cooling. It also circumvents infection and fluid overload with exacerbation of brain swelling that can be potentially encountered with cooling systems involving circulating the cerebrospinal fluid. Implanted catheters are prone to the complications of obstruction and infection. In order to circumvent these complications, strategies have been developed which include use of systemic or local antibiotics and impregnating catheter walls with antibiotics and metals. While these methodologies have shown some effectiveness, the risk of complications still remains high. Several catheters capable of delivering ultrasonic or laser energy for blood clot hemolysis have been described. There is no prior art for a catheter with the capability of selective brain hypothermia induction and ultrasound or laser energy use to maintain catheter patency. The use of ultrasound and/or laser energy along with anti-clotting and antimicrobial agents is also a novel concept and prevents catheter obstruction from blood clots and debris as well as infection.  
       SUMMARY OF THE INVENTION  
       [0009]     The invention provides a method and apparatus for performing selective hypothermia to the brain and/or the spinal cord for injury protection without the need for systemic cooling.  
         [0010]     For selective brain cooling, in one embodiment of the present invention, a flexible catheter is inserted into the cerebral lateral ventricle to cool the cerebrospinal fluid and henceforth brain. The catheter has three lumens with a distal heat conductive element which also has holes to allow for drainage of cerebrospinal fluid. Two lumens are connected at the tip of the catheter and allow for circulation of a coolant. The third lumen has holes at the distal end that allows for drainage of cerebrospinal fluid as well as intracranial pressure monitoring similar to a ventriculostomy. In another embodiment of this catheter, ultrasonic or laser energy is delivered either through the catheter wall or lumen. Catheters placed in the brain or ventricles carry a high risk of occlusion from blood as well as infection. Ultrasonic or laser energy provides clot lyses and maintains catheter patency. Impregnation of the catheter wall with anticoagulant/antithrombotic and antimicrobial agents which are slowly released also reduces the risk of catheter obstruction and infection.  
         [0011]     For selective spinal cord cooling, in another embodiment of the catheter described above, a catheter with a longer distal heat conductive element is inserted into the lumbar subdural or epidural space to allow for cooling around the spinal cord. This catheter may or may not have a lumen for drainage of cerebrospinal fluid.  
         [0012]     In another embodiment of the catheter, a balloon located at the distal end of the catheter expands when the coolant fluid is circulated. The expansion also opens the third lumen distal holes further to maintain patency.  
         [0013]     The catheters are designed to allow an inert coolant to circulate in the lumens without direct exposure to the brain or spinal cord and thereby altering the brain or spinal cord temperature. This allows for selective cooling of the brain and spinal cord for treatment of injury from trauma, ischemia, hypoxia and/or cerebral swelling. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0014]      FIG. 1  is a schematic view of the catheter in the brain ventricle.  
         [0015]      FIG. 2  is a top view of one embodiment of the catheter.  
         [0016]      FIG. 3  is a cross-sectional longitudinal view of the catheter taken along line A in  FIG. 2 .  
         [0017]      FIG. 4  is a cross-sectional longitudinal view of the catheter taken along line A in  FIG. 2 .  
         [0018]      FIG. 5  is a cross-sectional transverse view of the catheter taken along line B in  FIG. 2 .  
         [0019]      FIG. 6  is a cross-sectional side view of another embodiment of the catheter.  
         [0020]      FIG. 7  is a cross-sectional view of the catheter taken along line A in  FIG. 6 .  
         [0021]      FIG. 8  is a cross-sectional view of the catheter taken along line B in  FIG. 6 .  
         [0022]      FIG. 9  is a cross-sectional side view of another embodiment of the catheter.  
         [0023]      FIG. 10  is another cross-sectional side view of the catheter in  FIG. 9 .  
         [0024]      FIG. 11  is a cross-sectional view of the catheter taken along line A in  FIG. 10 .  
         [0025]      FIG. 12  is a cross-sectional side view of another embodiment of the catheter.  
         [0026]      FIG. 13  is a cross-sectional view of the catheter taken along line A in  FIG. 12 .  
         [0027]      FIG. 14  is a cross-sectional view of the catheter taken along line B in  FIG. 12 .  
         [0028]      FIG. 15  is a cross-sectional side view of another embodiment of the catheter.  
         [0029]      FIG. 16  is a cross-sectional side view of another embodiment of the catheter.  
         [0030]      FIG. 17  is a cross-sectional view of the catheter taken along line A in  FIG. 15 .  
         [0031]      FIG. 18  is a cross-sectional view of the catheter taken along line B in  FIG. 15 .  
         [0032]      FIG. 19  is a cross-sectional side view of another embodiment of the catheter.  
         [0033]      FIG. 20  is a cross-sectional view of the catheter taken along line A in  FIG. 19 .  
         [0034]      FIG. 21  is a cross-sectional view of the catheter taken along line B in  FIG. 19 .  
         [0035]      FIG. 22  is a cross-sectional side view of another embodiment of the catheter.  
         [0036]      FIG. 23  is a cross-sectional view of the catheter taken along line A in  FIG. 22 .  
         [0037]      FIG. 24  is a cross-sectional view of the catheter taken along line B in  FIG. 23 .  
         [0038]      FIG. 25  is a cross-sectional side view of another embodiment of the catheter.  
         [0039]      FIG. 26  is a cross-sectional view of the catheter taken along line A in  FIG. 25 .  
         [0040]      FIG. 27  is a cross-sectional view of the catheter taken along line B in  FIG. 25 .  
         [0041]      FIG. 28  is a cross-sectional side view of another embodiment of the catheter.  
         [0042]      FIG. 29  is a cross-sectional side view of another embodiment of the catheter.  
         [0043]      FIG. 30  is a cross-sectional side view of another embodiment of the catheter.  
         [0044]      FIG. 31  is a cross-sectional side view of another embodiment of the catheter.  
         [0045]      FIG. 32  is a cross-sectional view of the catheter taken along line A in  FIG. 28 .  
         [0046]      FIG. 33  is a cross-sectional view of the catheter taken along line B in  FIG. 28 .  
         [0047]      FIG. 34  is a cross-sectional side view of another embodiment of the catheter.  
         [0048]      FIG. 35  is a cross-sectional view of the catheter taken along line A in  FIG. 34 .  
         [0049]      FIG. 36  is a cross-sectional view of the catheter taken along line B in  FIG. 34 .  
         [0050]      FIG. 37  is a cross-sectional side view of another embodiment of the catheter.  
         [0051]      FIG. 38  is a cross-sectional view of the catheter taken along line A in  FIG. 37 .  
         [0052]      FIG. 39  is a cross-sectional view of the catheter taken along line B in  FIG. 37 .  
         [0053]      FIG. 40  is a cross-sectional side view of another embodiment of the catheter.  
         [0054]      FIG. 41  is a cross-sectional view of the catheter taken along line A in  FIG. 40 .  
         [0055]      FIG. 42  is a cross-sectional view of the catheter taken along line B in  FIG. 40 .  
         [0056]      FIG. 43  is a cross-sectional side view of another embodiment of the catheter.  
         [0057]      FIG. 44  is a cross-sectional view of the catheter taken along line A in  FIG. 43 .  
         [0058]      FIG. 45  is a cross-sectional view of the catheter taken along line B in  FIG. 43 .  
         [0059]      FIG. 46  is a cross-sectional side view of another embodiment of the catheter.  
         [0060]      FIG. 47  is a cross-sectional side view of another embodiment of the catheter.  
         [0061]      FIG. 48  is a cross-sectional side view of another embodiment of the catheter.  
         [0062]      FIG. 49  is a cross-sectional side view of another embodiment of the catheter.  
         [0063]      FIG. 50  is a cross-sectional view of the catheter taken along line A in  FIG. 49 .  
         [0064]      FIG. 51  is a cross-sectional view of the catheter taken along line B in  FIG. 49 .  
         [0065]      FIG. 52  is a cross-sectional side view of another embodiment of the catheter.  
         [0066]      FIG. 53  is a cross-sectional view of the catheter taken along line A in  FIG. 52 .  
         [0067]      FIG. 54  is a cross-sectional view of the catheter taken along line B in  FIG. 52 .  
         [0068]      FIG. 55  is a cross- sectional side view of another embodiment of the catheter.  
         [0069]      FIG. 56  is a cross-sectional view of the catheter taken along line A in  FIG. 55 .  
         [0070]      FIG. 57  is a cross-sectional view of the catheter taken along line B in  FIG. 55 .  
         [0071]      FIG. 58  is a cross-sectional side view of another embodiment of the catheter.  
         [0072]      FIG. 59  is a cross-sectional view of the catheter taken along line A in  FIG. 58 .  
         [0073]      FIG. 60  is a cross-sectional view of the catheter taken along line B in  FIG. 58 .  
         [0074]      FIG. 61  is a top view of the bolt.  
         [0075]      FIG. 62  is a cross-sectional view of the outer bolt sheath.  
         [0076]      FIG. 63  is another top view of the bolt.  
         [0077]      FIG. 64  is a cross-sectional view of the sheath connected to the bolt. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0078]     In one method of selective brain and/or spinal cooling, a catheter as shown in  FIG. 1 , can be placed into the ventricle of the brain or the subdural space of the spine. This allows for cooling of the cerebrospinal fluid and hence the brain and/or spinal cord selectively. These catheters can be placed in the lateral ventricles using the standard landmarks or can be precisely placed with stereotactic guidance or use of an endoscope. The bolt  4  secures the catheter  5  to the skull  1 . The catheter  5  is placed into the cerebrospinal fluid in the ventricle  3 .  
         [0079]     As illustrated in  FIG. 2 , the catheter has a proximal portion  6  and a distal heat transfer element  7 . The distal heat transfer element  7  has several circumferential holes  8  that allow drainage of cerebrospinal fluid as well as monitoring of intracranial pressure.  
         [0080]     In one embodiment of the cooling catheter as shown in  FIGS. 3-5 , the heat exchange fluid or compressed refrigerant enters through the central lumen  8  into the distal end of the heat transfer element  9 . The coolant or the gaseous refrigerant returns through the outer lumen  10 . The circulation of the coolant through the catheter cools the distal heat transfer element, thereby allowing the cerebrospinal fluid surrounding the catheter to be cooled. Lumen  11  provides for drainage of the cerebrospinal fluid through the holes  12 . The heat transfer element  13  is also capable of expanding like a balloon when fluid under pressure is circulated through lumen  10 .  
         [0081]     In another embodiment of the cooling catheter as shown in  FIGS. 6-8 , a coolant enters through lumen  14  into the distal end of the catheter and returns through lumen  15 . The lumens  14  and  15  are separated by a membrane  16 . The central lumen  17  allows drainage of the cerebrospinal fluid through the holes  18 .  
         [0082]     In another embodiment of the cooling catheter as shown in  FIGS. 9-11 , a coolant enters into the distal end of the catheter through lumen  19  and returns through lumen  20 . The distal catheter end  21  is capable of expanding like a balloon to increase the surface area of heat transfer when the coolant is circulated under pressure.  
         [0083]     In another embodiment of the cooling catheter as shown in  FIGS. 12-14 , a coolant is circulated through central lumens  22  and  23  in the catheter which communicate at the distal end  24 . Lumen  25  allows drainage of the cerebrospinal fluid through the holes  26  in the catheter wall  27 .  
         [0084]      FIGS. 15-18  illustrate an ultrasonic catheter system also capable of cooling. The distal catheter wall  28  as seen in  FIG. 16  or the wall  28  and tip  29  as seen in  FIG. 15  contain the ultrasound transducer with a piezoelectric crystal  30  surrounded by electrodes  31 . The catheter contains three lumens. The central lumen  32  communicates with the outer lumen  33  at the distal end  34  and circulates a coolant to dissipate the heat generated from the ultrasound and also cool the brain. The intermediate lumen  35  contains ports  36  at the distal end that communicate with the external environment. When the catheter lumen becomes obstructed from a blood clot or debris, the ultrasonic energy dissolves the clot which can be further facilitated if needed by infusing a hemolytic or thrombolytic or antiplatelet agent through lumen  35  and then draining the liquefied blood through the same lumen. Since this lumen communicates with the brain, it can also be used to monitor the intracranial pressure.  
         [0085]      FIGS. 19-21  illustrate an ultrasonic catheter with the transducer at the distal tip  37 . The ultrasound transducer electrodes  38  are embedded in the catheter wall. The catheter contains three lumens. The central lumen  39  communicates with the outer lumen  40  at the distal end  41  and circulates a coolant. The intermediate lumen  42  contains ports  43  at the distal portion of the catheter.  
         [0086]      FIGS. 22-24  illustrate another embodiment of the ultrasonic cooling catheter. The catheter contains two lumens separated by an ultrasound transducer. The inner lumen  47  communicates with the outside environment through ports  46 . The outer lumen  48  is split into two halves by the wall  49  which communicate at the distal end  50  and allow for a coolant to circulate. The ultrasound transducer is embedded between the two lumens and contains the piezoelectric element  44  and the electrode  45 .  
         [0087]     In another embodiment of the ultrasonic cooling catheter as illustrated in  FIGS. 25-27 , the outer lumen  51  contains ports  52  to drain fluid or blood. The inner lumen  53  contains a wall  54  and split&#39;s the lumen into two halves which communicate at the distal end  55  to allow circulation of a coolant. The ultrasound transducer embedded between these lumens contains the piezoelectric element  56  with the electrodes  57  along with an amplifier  58 .  
         [0088]     In another embodiment of the ultrasonic cooling catheter as illustrated in  FIGS. 28-33 , the catheters contain two lumens  59  and  60 . The outer lumen  60  is split into two halves by the wall  61  which communicate at the distal end  62  and allow for a coolant to circulate. The inner lumen  59  communicates with the outside environment through ports  63 . The lumen  59  is also capable of incorporating an ultrasound transducer or conductor  64  which is removable. This catheter would be more suited for dissolving clots or obstructions in the catheter through ultrasonic energy and maintain catheter patency with periodic use.  FIG. 30  illustrates a similar catheter with an anchor  65  at the distal end for the removable ultrasound transducer or conductor  64 . This anchor can also serve as an amplifier for the ultrasound energy.  FIG. 31  illustrates the catheter with the ultrasound transducer removed.  
         [0089]      FIGS. 34-36  illustrate a laser catheter system also capable of cooling. The distal catheter wall  66  contains optical fibers  67 . The central catheter lumen  68  communicates with the outer environment through ports  69 . The catheter wall contains a lumens  70  and  71  divided into two halves by a wall  72  which communicate at the distal end  73 . A coolant is circulated through the lumens  70  and  71  to dissipate the heat generated from the laser and also cool the brain. The laser energy dissolves the clot obstructing the catheter lumen  68  which can be further facilitated if needed by infusing a hemolytic or thrombolytic or antiplatelet agent through lumen  68  and then draining the liquefied blood through the same lumen. Since this lumen communicates with the brain, it can also be used to monitor the intracranial pressure.  
         [0090]     In another embodiment as illustrated in  FIGS. 37-39 , the catheter wall  74  contains optical fibers  75  that are coupled to a laser source and transmit energy to dissolve clotted blood in the brain. The catheter contains three lumens. The central lumen  76  communicates with the outer lumen  77  at the distal end  78  and circulate a coolant to cool the cerebrospinal fluid and/or brain and also dissipate the heat generated from the laser energy. The middle lumen  79  contains ports  80  at the distal end that allow drainage of blood and/or cerebrospinal fluid. The lumen  79  can also be used to administer medications or agents to facilitate blood dissolution and/or neuroprotection.  
         [0091]     In another embodiment as shown in  FIGS. 40-42 , the catheter contains two lumens. The outer lumen  81  is divided into two halves by a wall  82  and communicate at the distal end  83 . A coolant is circulated through lumen  81  to cool the brain or spinal cord. The central lumen  84  contains ports  85  at the distal end. Removable optical fibers  86  can be inserted into the lumen  84  as needed to dissolve clotted blood.  
         [0092]      FIGS. 43-45  illustrate a catheter with optical fibers in the wall  87 . The wall also contains ports  88  that communicate with the lumen  89 . The central lumen  90  is divided into two halves by a wall  91  that communicate at the distal end  92  and allows for circulation of a coolant.  
         [0093]     A catheter system providing for central nervous system cooling while also incorporating the ultrasound and laser energy to dissolve and drain blood clots from the central nervous system and maintain catheter patency is illustrated in  FIGS. 46-4  As shown in  FIG. 46 , the catheter wall contains optical fibers  92  along with ports  93  that communicate with the lumen  94 . The ultrasound transducer contains a piezoelectric element  95  surrounded by electrodes  96  and  97 . In another embodiment as shown in  FIG. 48 , the catheter also contains a central lumen  98  that communicates at the distal end  99  with lumen  100  and allows for a coolant to circulate to cool the central nervous system and also dissipate heat generated from the lasers and ultrasound. In another embodiment as shown in  FIG. 47 , the catheter wall contains optical fibers  101  along with ports  102  that communicate with the lumen  107 . The ultrasound transducer  106  is surrounded by the lumen  107 . The catheter also contains lumens  103  and  105  that communicate at the distal end  104  and circulate a coolant.  
         [0094]      FIGS. 49-51 , illustrate a catheter with optical fibers  108  in the outer wall that also contains ports  109  at the distal end that connect the outer environment to the lumen  110 . The lumen  110  also contains the ultrasound transducer  111 . The catheter wall also contains lumens  112  and  113  which are split by a wall  114  that allows communication between the two lumens at the distal end  115 . A coolant is circulated through lumens  112  and  113  to cool the central nervous system and also dissipate heat generated from the lasers and ultrasound.  
         [0095]     In another embodiment as shown in  FIGS. 52-54 , the catheter wall contains the ultrasound transducer with the piezoelectric element  116  surrounded by the electrodes  117  and  118 . The distal end of the catheter wall also contains ports  119  that communicate with the lumen  120 . The central lumen  120  contains the laser optical fibers  121 . The lumen  122  is split by a wall  123  that allows communication at the distal end  124  and circulates a coolant. In another embodiment as illustrated in  FIGS. 55-57 , the catheter wall contains the ultrasound transducer  125  with ports  126  that connect with the lumen  127 . The lumen  127  contains another lumen  128  which harbors the optical fibers  129  and also circulates a coolant which connects with the outer lumen  130  at the distal end  131 . In another embodiment illustrated in  FIGS. 58-60 , the catheter contains laser optical fibers  132  embedded in the wall and ports  133  communicating with the lumen  134 . The central lumen  135  is split in two halves by a wall  136  that connect at the distal end  137  and circulate a coolant. The ultrasound transducer  138  surrounds the central cooling lumen  135 .  
         [0096]      FIGS. 61-64  illustrate a bolt used to secure the catheter to the skull. The T-shaped bolt as seen in  FIG. 61  comprises of threads  142  which secure to a hole drilled in the skull and threads  139  that secure the outer sheath  143 . The bolt also contains handles  141  and slits  140 . The outer sheath  143  also contains threads  144  as shown in  FIG. 62 . As illustrated in  FIG. 63  the slits  140  are capable of closing when the outer sheath is secured and tightened to the bolt.  FIG. 63  illustrates the bolt  146  with the outer sheath  143  secured. The sheath threads  144  are secured to the bolt threads  139  and when tightened lead to the closure of the slits  140  which compresses the bolt wall to narrow the bolt opening  145  and secures the catheter  146  to the bolt.  
         [0097]     While the methodology described herein is specific for central nervous system cooling and prevention of catheter obstruction and infection, its use is not limited to this particular pathology. These catheters can also be used to treat various other central nervous system pathologies. For instance, ultrasonic and/or laser energy directly transmitted into a brain blood clot or tumor with the catheter system allows for clot hemolysis and drainage as well as tumefaction and dissolution of the tumor cells which can then be drained directly. Similarly heat or cold variation through the catheter can also facilitate the tumefaction process along with a direct delivery of a chemotherapeutic agent.