Patent Publication Number: US-2012031405-A1

Title: Methods and systems for cerebral cooling

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     A claim for the benefit of priority under 35 U.S.C. §119(e) is hereby made to the Jun. 7, 2010, filing of U.S. Provisional Patent Application 61/352,295, titled “METHODS AND SYSTEMS FOR CEREBRAL COOLING,” the entire disclosure of which is, by this reference, hereby incorporated herein. 
    
    
     TECHNICAL FIELD 
     The present invention relates generally to systems and methods for treating decreased blood flow to or through the brain, or cerebral hypoperfusion, which might occur in cerebral vascular accidents, such as stroke, cardiac arrest and traumatic brain injuries. In particular, the present invention relates to systems and methods that employ cooling techniques to stabilize a subject when cerebral hypoperfusion is suspected; for example, following a suspected cerebral vascular accident. Even more specifically, the present invention relates to methods in which cooled air or cooled, oxygen-rich gas is forced into the nasal cavity of a subject, and optionally into the subject&#39;s paranasal sinuses, to cool the subject&#39;s brain, as well as to systems that are configured to effect such a method. Some embodiments of the present invention, furthermore, include the simultaneous delivery of Continuous Positive Airway Pressure (CPAP) oxygen enriched, cooled gas to the lungs. 
     SUMMARY 
     The present invention, in one aspect, includes methods for cooling, or lowering a temperature of, the brain of a subject. These methods may also be referred to as “cerebral cooling” methods. Brain cooling methods that incorporate teachings of the present invention may be useful for treating a decrease in the flow of blood through the brain, which is known in the art as “cerebral hypoperfusion.” Cerebral hypoperfusion may occur during a cerebral vascular accident, such as a stroke, a traumatic brain injury, or cardiac arrest, or with other conditions that may restrict or otherwise decrease the flow of blood into the brain. 
     In a various embodiments of a brain cooling method of the present invention, air, oxygen (O 2 ) or a gas mixture that includes elevated levels of oxygen (i.e., more than about 20.9, by molar content per volume) is cooled to a temperature below the normal body temperature (e.g., about 37° C., etc.) of a subject to whom the oxygen or gas mixture is to be administered. For the sake of simplicity, air, oxygen, and gas mixtures that include elevated levels of oxygen are also collectively referred to herein as “respiratory gas.” Respiratory gas that comprises substantially pure oxygen, as well as respiratory gas that includes above-normal amounts of oxygen (e.g., greater than about 20.9%, by molar content per volume, etc.), are also referred to herein as “oxygen-rich gas.” The respiratory gas may be administered under a positive pressure, which may exceed the normal, physiologic air pressure generated as the subject inhales spontaneously, on his or her own. In addition, the respiratory gas may be administered at a flow rate that exceeds the rate at which the subject normally inhales air. In some embodiments, the respiratory gas may be administered under continuous positive airway pressure. The manner in which cooled respiratory gas is delivered may provide control over and, thus, enable programming of, the rate at which a subject&#39;s brain (and body) are cooled. 
     The present invention also includes various embodiments of methods for returning the temperature of a subject&#39;s brain to a state of normal thermia (e.g., normal body temperature). These methods may also be referred to as “rewarming” methods. Rewarming may be effected at a rate that is programmed or otherwise controlled in such a way as to prevent a subject from entering into a state of shock. 
     Techniques of the present invention may also be used to control the core temperature of a subject&#39;s body. Cooling and/or rewarming of a subject&#39;s core temperature may also be effected at a controlled rate. 
     In another aspect, the present invention includes various embodiments of brain cooling systems. A brain cooling system of the present invention includes a gas delivery system and a cooling apparatus. The gas delivery system may include an oxygen source, an apparatus for establishing a desired pressure and flow rate for respiratory gas to be inhaled by a subject, and an interface element. The interface element receives respiratory gas from the pressurization element through an inspiratory breathing tube. In some embodiments, the pressurization element may comprise a continuous positive airway pressure (CPAP) device. The interface element, which receives respiratory gas from the pressurization element through an inspiratory breathing conduit, may include a breathing mask. Such a brain cooling system may be used to treat cerebral hypoperfusion, as may occur during a cerebral vascular accident (CVA), such as a stroke, traumatic brain injury, or cardiac arrest, or with any other condition that may inhibit or slow the flow of blood to a subject&#39;s brain and, therefore, may result in a CVA or, more broadly, in cerebral hypoperfusion. 
     Some embodiments of brain cooling systems that incorporate teachings of the present invention may also include temperature monitoring apparatus. The temperature monitoring apparatus may be configured to determine the temperature of a subject&#39;s brain, the subject&#39;s core temperature, or both the brain temperature and the core temperature of the subject. 
     A brain cooling system of the present invention may be configured to rewarm a subject&#39;s body and/or to maintain the subject&#39;s core temperature at or above a predetermined temperature. Warming may be effected by the cooling apparatus, or by a separate heating component. 
     In an additional aspect, the present invention includes a cooling apparatus. A cooling apparatus of the present invention, which may be used in conjunction with a brain cooling system, includes a conduit and a cooling element within the conduit. The cooling element may, in some embodiments, include a substrate that carries a channel through which a heat transfer fluid may flow. The elongate channel may travel a path that extends across various locations of an area of the substrate (e.g., a serpentine path, a meandering path, etc.). The path includes an inlet end, into which a cooled heat transfer fluid may flow, as well as an outlet end out of which a warmer heat transfer fluid may flow. The cooling element may be folded (e.g., in an accordion-like arrangement, rolled, etc.) to facilitate its placement within the conduit. When placed within the conduit in a folded configuration, the cooling element may define one or more narrow passages that extend along at least a portion of the length of the conduit in a way that enables fluid, such as respiratory gas, to flow through the conduit. Such a folded configuration of the cooling element may increase an internal surface area within a portion of the conduit. In addition to the conduit and the cooling element, a cooling apparatus of the present invention may include a fluid refrigeration apparatus for cooling the heat transfer fluid, as well as a cool fluid transfer conduit for providing cooled heat transfer fluid from the outlet of the refrigeration apparatus to the inlet end of the channel of the cooling element and a warm fluid transfer conduit for transporting warmer heat transfer fluid from the outlet end of the channel of the cooling element to the inlet of the refrigeration apparatus. 
     Other aspects and embodiments, as well as features and advantages of various aspects and embodiments, of the present invention will become apparent to those of skill in the art through consideration of the ensuring description, the accompanying drawings, and the appended claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the drawings: 
         FIG. 1  is a schematic representation of an embodiment of a brain cooling system that incorporates teachings of the present invention; 
         FIG. 2  is a top view of an embodiment of a cooling apparatus that may be included in a system such as that shown in  FIG. 1 ; 
         FIG. 3  is a cross-sectional view of the cooling apparatus of  FIG. 2 , taken along line  3 - 3  of  FIG. 2 ; and 
         FIG. 4  is illustrates the embodiment of cooling apparatus of  FIGS. 2 and 3  in a rolled configuration, disposed within a conduit; for example, the conduit of a brain cooling system such as that depicted by  FIG. 1 . 
     
    
    
     DETAILED DESCRIPTION 
     With reference to  FIG. 1 , an embodiment of a brain cooling system  10  is illustrated. Brain cooling system  10  includes a gas delivery system  20  and a cooling apparatus  40 . The gas delivery system  20  of a brain cooling system may include a pressurization apparatus  25  and an interface element  30 , which is configured to deliver cooled air or gas under positive pressure to the nasal cavity of a subject. 
     The pressurization apparatus  25  of a gas delivery system  20  of a brain cooling system  10  of the present invention may receive air, oxygen, or an oxygen-rich mixture of gases from a source  22 . The source  22  may comprise a source of substantially pure oxygen (e.g., a gas tank, etc., containing the oxygen), the atmosphere, or a combination of the source of oxygen and the atmosphere. Such respiratory gas may be communicated from the source  22  to an inlet  24  of the pressurization apparatus  25  through a source conduit  23 , as illustrated, or directly. In some embodiments, the pressurization apparatus  25  may also draw air from its surrounding environment. In such an embodiment, the air may be mixed with the oxygen or oxygen-rich mixture of gases from the source  22 . 
     The pressurization apparatus  25  compresses the respiratory gas so that it may be delivered, under positive pressure, to an outlet  26  of the pressurization apparatus, and through an inspiratory breathing conduit  29  that communicates with the interface element  30 . In some embodiments, the inspiratory breathing conduit  29  may be coupled directly to the outlet  26  of the pressurization apparatus  25 . 
     More specifically, the pressurization apparatus  25  of a gas delivery system  20  of a brain cooling system  10  of the present invention may be configured to compress the respiratory gas to a pressure that exceeds the “normal” physiologic pressure of a subject&#39;s airway. The pressurization apparatus  25  may be configured to compress the respiratory gas to a pressure of about 0.5 kPa or more. In some embodiments, the pressurization apparatus  25  may compress the respiratory gas to a pressure of up to about 2 kPa. 
     Additionally, in some embodiments of a gas delivery system  20 , the pressurization apparatus  25 , its outlet  26 , and the inspiratory breathing conduit  29  that communicates with the outlet  26  may be configured to deliver the respiratory gas at a flow rate of at least about 25 liters per minute (e.g., 30 liters per minute, 50 liters per minute, 60 liters per minute, etc.). In some embodiments, respiratory gas may be delivered at a rate of up to about 150 liters per minute. 
     Compression of the oxygen-rich gas may be effected in a substantially continuous manner, such that the pressurization apparatus  25  may deliver, through its outlet  26 , respiratory gas at a substantially constant positive pressure. Without limiting the scope of the present invention, the phrase “substantially constant,” when used in conjunction with “positive pressure,” includes variations of about 10% or less from a predetermined positive pressure. 
     Moreover, the respiratory gas may be delivered by the pressurization apparatus  25  at a substantially constant rate of flow. “Substantially constant,” when used in reference to “rate of flow” or “flow rate,” includes, but is not limited to, flow rates that vary by no more than about 10% from a predetermined flow rate. 
     In a specific embodiment, the pressurization apparatus  25  comprises a continuous positive airway pressure (CPAP) apparatus. In such an embodiment, the interface element  30  may be configured to deliver a constant, uninterrupted (e.g., by exhalation, etc.) flow of cooled respiratory gas to the nasal cavity of a subject. The interface element  30  may comprise a nasal mask (e.g., a so-called “nasal non-invasive ventilation mask,” or “nasal NIV mask,” etc.), which is configured for placement over a portion of a subject&#39;s face. As an alternative, a so-called “nostril occlusive nasal delivery device” (e.g., nasal prongs, a cannula style bi-level positive airway pressure (BiPAP) mask, nasal pillows, etc.) are useful as interface elements  30  with CPAP apparatuses. 
     Alternatively, the pressurization apparatus  25  may be a transport ventilator. When used to deliver cooled respiratory gas to a subject, a transport ventilator may operate in a non-invasive positive pressure ventilation (NPPV) mode. Of course, other suitable devices may also serve as the pressurization apparatus  25  of a gas delivery system  20  that may be employed by a brain cooling system  10  of the present invention. 
     The cooling apparatus  40  of a brain cooling system  10  that incorporates teachings of the present invention is associated with the gas delivery system  20  in such a way as to cool respiratory gas before the respiratory gas is delivered to a subject. In some embodiments, the cooling apparatus  40  may be located upstream of the pressurization apparatus  25 . In other embodiments, such as that depicted by  FIG. 1 , the cooling apparatus  40  may be located downstream from the pressurization apparatus  25 , between the pressurization apparatus  25  and the interface element  30 . The cooling apparatus  40 , or the location at which the cooling apparatus  40  cools the respiratory gas to be inhaled by a subject, may even be located just upstream (e.g., within about 18 inches, within about 12 inches, etc.) from the interface element  30 , or from a location at which respiratory gas enters the nasal cavity of the subject. Placement of the cooling apparatus  40  in such close proximity to the nasal cavity may minimize the transfer of heat into the respiratory gas as it travels between the location where it is cooled (e.g., at the cooling apparatus  40 ) and the subject&#39;s nasal cavity, which may increase, and even optimize, the efficiency of the brain cooling system  10 . 
     The cooling apparatus  40  may be configured to cool the respiratory gas to a desired, or predetermined, temperature (e.g., about 1° C., up to about 35° C., about 10° C. to about 20° C., about 15° C., etc.) or to a temperature within a desired range of temperatures. In some embodiments, the cooling apparatus  40  may utilize known convective heat transfer methods. As an example, the cooling apparatus  40  may include a radiator, heat sink-type configuration that removes heat from the respiratory gas and transfers that heat to the external environment. In some embodiments, the cooling apparatus  40  may employ a coolant (e.g., FREON, etc.). In other embodiments, the cooling apparatus  40  may use one or more thermoelectric Peltier effect devices, such as those manufactured by Tellurex Corporation of Traverse City, Mich., to draw heat directly from a radiator/heat sink. 
     Another specific embodiment of cooling apparatus  40 ′ that may be used in a brain cooling system  10  of the present invention is illustrated by  FIGS. 2-4 . Cooling apparatus  40 ′ includes a conduit  41 ′ and a cooling element  42 ′ configured to be disposed within the conduit  41 ′. Cool and warm fluid transport conduits  46 ′ and  47 ′ enable circulation of a heat transfer fluid  48 ′ between the cooling element  42 ′ and the fluid refrigeration apparatus  49 ′. 
     The conduit  41 ′ may comprise part of the source conduit  23  or of the inspiratory breathing conduit  29  of the gas delivery system  20  ( FIG. 1 ). Alternatively, the conduit  41 ′ may be configured to be coupled to the source conduit  23  or the inspiratory breathing conduit  29 , either at an intermediate location or at an end of the source conduit  23  or the inspiratory breathing conduit  29 . 
     A specific embodiment of the cooling element  42 ′, which is shown in  FIGS. 2 and 3 , includes a substrate  43 ′ that carries at least one channel  45 ′. The substrate  41 ′ may comprise a pair of laminated thin sheets or films  43   a ′,  43   b ′. Each thin sheet or film  43   a ′,  43   b ′ may have a sufficient area to be folded or rolled into an element that may be disposed within, and occupy a significant portion (e.g., at least about ¼, at least about ⅓, at least about ½, at least about %, up to about ¾, etc.) of a cross-sectional area of the conduit  41 ′, as illustrated by  FIG. 4 . Without limiting the scope of the present invention, each thin sheet or film  43   a ′,  43   b ′ of the substrate  43 ′ may be formed from a polymer, such as the biaxially-oriented polyethylene terephthalate (boPET) polyester film marketed by E.I. du Pont de Nemours and Company as MYLAR®. 
     One of the thin sheets or films  43   b ′ may define the at least one channel  45 ′. As a non-limiting example, each channel  45 ′ may be formed (e.g., thermally, etc.) into the thin sheet or film  43   b ′, which may then be secured (e.g., by an adhesive, by thermal bonding, etc.) adhered to the other thin sheet or film  43   a ′ to complete each channel  45 ′. Thermal conductivity of the substrate  41 ′ may be enhanced by providing a film  43   c ′ (e.g., laminating a preformed film  43   c ′, forming a film  43   c ′ by a vapor deposition process, forming a film  43   c ′ by sputtering, etc., as known in the art) comprising a more thermally conductive material (e.g., a metal, such as aluminum, etc.) to at least one of the thin sheets or films  43   a ′ or  43   b ′, such as over the protruding areas of thin sheet or film  43   b ′ that define each channel  45 ′. 
     The channel  45 ′ formed between thin sheets or films  43   a ′ and  43   b ′ includes an inlet end  45   i ′ and an opposite outlet end  45   o ′. The cool fluid transport conduit  46 ′ establishes communication between an outlet  49   o ′ of the fluid refrigeration apparatus  49 ′ and the inlet end  45   i ′ of the channel  45 ′, while the warm fluid transport conduit  47 ′ establishes communication between the outlet end  45   o ′ of the channel  45 ′ and an inlet  49   i ′ of the fluid refrigeration apparatus  49 ′. 
     The fluid refrigeration apparatus  49 ′ may comprise a thermoelectric liquid chiller, such as that available from Solid State Cooling Systems of Wappingers Falls, N.Y., as the OASIS  160 , or any other refrigeration device that may cool a heat transfer fluid  48 ′ to a desired temperature (e.g., from about 1° C. to about 35° C., about 10° C. to about 20° C., about 15° C., etc.). 
     With returned reference to  FIG. 1 , the brain cooling system  10  may also include one or more temperature sensors  50 ,  52 . A temperature sensor  50  may be associated with some feature of the brain cooling system  10  (e.g., the cooling apparatus  40 , the interface element  30 , etc.). Alternatively, a temperature sensor  52  may be configured for use in directly monitoring the subject&#39;s temperature (e.g., a so-called “physiologic tunnel,” such as a medial canthal area on a subject&#39;s face (i.e., near the medial corner of each of the subject&#39;s eyes), which provides a direct measure of brain temperature; eardrum, or tympanic membrane temperature; temperature within the nasal cavity, etc.). 
     A temperature sensor  50  associated with a feature of the brain cooling system  10  may be configured to provide a measure of the temperature of respiratory gas. Without limiting the scope of the present invention, a temperature sensor  50  may be positioned at or adjacent to a location of the interface unit  30  where respiratory gas exits the interface unit and/or enters the nasal cavity of a subject. Such an arrangement may enable monitoring of a temperature the respiratory gas at a point of contact with the subject. 
     Direct monitoring of a subject&#39;s temperature may comprise a non-invasive measurement of the subject&#39;s brain temperature, in which case the temperature sensor  52  may comprise an apparatus configured to sense temperature at a physiological tunnel (e.g., a terminal branch of the superior ophthalmic vein, etc.) that communicates the temperature of the subject&#39;s brain to a location at or near a surface of the subject&#39;s body. While a variety of apparatuses may be configured to obtain such a measurement and are, therefore, within the scope of the present invention, specific examples of such a temperature sensor  52  are provided by U.S. Pat. No. 7,187,960 to Abreu, the entire disclosure of which is, by this reference, hereby incorporated herein. 
     As another non-limiting example, devices that sense microwaves emitted by a subject&#39;s brain may be used to directly and non-invasively monitor the temperature of the subject&#39;s brain. Such a device passively senses microwaves, which are emitted from the brain with intensities that correspond to the temperature of the brain. An embodiment of such a device is described by Bass, W. T., et al., “Brain Temperature Measurement by Radiometric Thermometry in Normal Term Infants and Infants Treated with Moderate Systemic Hypothermia for Hypoxic-Ischemic Encephalopathy,” Pediatric Academic Soc./Asian Soc. For Ped. Res. Joint Mtg.—Denver, Colo., USA (2011) and by “Researchers develop device to measure brain temperature non-invasively,” EurekAlert!, http://www.eurekalert.org/pub_releases/2011-05/chot-rdd50211.php (May 2, 2011), the entire disclosures of both of which are hereby incorporated herein, in their entireties, by this reference. 
     The temperature sensor  52  of a brain cooling system  10  of the present invention may be configured to provide a measure of the core temperature of a subject&#39;s body. By way of non-limiting example, a temperature sensor  52  that is configured to monitor the temperature of a subject&#39;s tympanic membrane may provide an indication of the subject&#39;s core temperature. 
     Measurements of the temperature within a subject&#39;s nasal cavity may be obtained by use of a temperature sensor  52  that is configured to be disposed within the subject&#39;s nasal cavity and to contact a surface of the subject&#39;s nasal cavity. 
     Of course, a brain cooling system  10  of the present invention may include one or more temperature sensors  52  that are configured to monitor any of the brain temperature, core temperature, nasal cavity temperature, any other useful temperature or any combination of the foregoing. 
     It may be desirable to include a humidification component  55  in a brain cooling system  10 . A humidification component  55  may be configured to introduce humidity (e.g., water vapor, a mist, etc.) into the nasal cavity of the subject. Humidification of tissues in the nasal cavity may be desirable to counteract the drying that may occur with the prolonged introduction of dry respiratory gas into the subject&#39;s nasal cavity. Humidification may also facilitate evaporative cooling of the tissues of the nasal cavity and, thus, expedite cooling of the brain. 
     The humidification component  55  may be configured to operate in accordance with a program, in response to feedback provided by other components of the brain cooling system  10  (e.g., a humidity monitor, which may be separate from or combined with a temperature monitor, etc.) or on demand. Moisture may be provided continuously or intermittently (e.g., in a pulsed manner; i.e., at a constant or substantially constant frequency; etc.) by the humidification component  55 . In some embodiments, the humidification component  55  may be associated with (e.g., communicate humidity to, etc.) the gas delivery system  20  of the brain cooling system  10 . 
     Continuing reference to  FIG. 1 , in addition to being configured to cool a subject&#39;s brain, brain cooling system  10  may include one or more warming elements, which are configured to warm parts of a subject&#39;s body. Without limitation, a brain cooling system  10  may be equipped to increase the temperature of a subject&#39;s brain. Alternatively, or in addition, a brain cooling system  10  may include one or more components for managing a subject&#39;s core temperature. 
     A rewarming element  57  may enable use of brain cooling system  10  to facilitate a post-cooling increasing the temperature of a subject&#39;s brain, or “rewarming.” In some embodiments, the rewarming element  57  may comprise an element configured to heat respiratory gas. Such a rewarming element  57  may communicate with the gas delivery system  20 , which may introduce heated respiratory gas (relative to the temperature of the previously delivered cool respiratory gas and, in some embodiments, gradually increasing over time) into the subject&#39;s nasal cavity. In some embodiments, the cooling apparatus  40  may also serve as a rewarming element  57 . By way of non-limiting example, in embodiments where the cooling apparatus  40  comprises one or more thermoelectric Peltier effect devices, reversal of electrical current through the cooling apparatus heats, rather than cools, the side of the cooling apparatus  40  against which respiratory gas flows. Although the rewarming element  57  is depicted in  FIG. 1  as comprising at least a part of the same element as the cooling apparatus  40 , the cooling apparatus  40  and the rewarming element  57  may comprise separate elements. In embodiments where respiratory gases may not be cooled and heated at the same location, the gas delivery system  20  of the brain cooling system  10  may enable tailoring of the temperature of respiratory gas by enabling the selective flow of respiratory gas through or past cooling elements and/or heating elements. 
     A body warming element  59  may enable management of subject&#39;s core body temperature while other components (e.g., any combination of the cooling element  40 , any rewarming element  57  and/or the gas delivery system  20 , etc.) of the brain cooling system  10  control the subject&#39;s brain temperature. In a specific embodiment, the body warming element  59  may be configured to prevent cooling of a subject&#39;s body to hypothermic levels (e.g., a temperature of less than 32° C., etc.) while cooling the subject&#39;s brain. A non-limiting example of a body warming element  59  includes a warming blanket or pad. 
     Some embodiments of a brain cooling system  10  may also include a control system  60 , which may comprise a processing element  62 , such as a computer processor and associated memory, a microcontroller, or the like. The processing element  62  may be programmed to control operation of at least one of the pressurization apparatus  25 , the cooling apparatus  40 , any humidification component  55 , any rewarming element  57 , any body warming element  59 , and one or more other elements of the brain cooling system  10 . By controlling operation of one or more of the pressurization apparatus  25 , the cooling apparatus  40  and other components of the brain cooling system  10 , the control system  60  may provide control (e.g., enable programming, etc.) over the rate and/or extent of cooling and/or heating. 
     In addition to the processing element  62 , a control system  60  of a brain cooling system  10  of the present invention may also include an input/output element  64  of a known type. The input/output element  64  may communicate with the processing element  62  in a way that enables a user to control operation of one or more other elements of the brain cooling system  10 , such as the pressurization apparatus  25 , the cooling apparatus  40 , and/or another element of the brain cooling system  10 . 
     In the depicted embodiment, the control system  60  is part of the cooling apparatus  40 . The input/output element  64  may enable a user to select a desired temperature to which the respiratory gas will be cooled, or even to which the brain will be cooled. When a user enters such a selection (e.g., a target temperature, etc.) into the input/output element  64 , the input/output element  64  generates and transmits signals to the processing element  62 , which then correspondingly increases or decreases a temperature of the cooling apparatus  40 , causing the cooling apparatus  40  to operate in the manner desired by the user. Conversely, the processing element  62  may, in conjunction with one or more sensors or monitors of the brain cooling system, monitor one or more parameters (e.g., the temperature at a specific location of or adjacent to the cooling apparatus  40 ; the temperature monitored by a sensor  50 ,  52  associated with the interface element  30  or the subject; the humidity within the subject&#39;s nasal cavity; etc.) and, in some embodiments, based on the information, or feedback, provided by such monitoring, provide one or more alarms that enable an individual to manually adjust the delivery of respiratory gas or automatically control operation of one or more features of the cooling apparatus  40  in response to the monitored parameter or parameters (e.g., the temperature of respiratory gas; preventing hypothermia as brain cooling continues, etc.). 
     Alternatively, or in addition, the pressurization apparatus  25  may include or have associated therewith a control system  60 ′. In some embodiments, the control system  60 ′ associated with the pressurization apparatus  25  may include a processing element  62 ′ and an input/output element  64 ′. The input/output element  64 ′ may enable a user to select one or more of a desired gas mixture (e.g., a particular amount of oxygen), a desired pressure, and a desired flow rate of the respiratory gas to be delivered by the pressurization apparatus  25 . Upon receiving a particular input command, the input/output element  64 ′ may generate corresponding signals, which are transmitted to the processing element  62 ′. Those signals are then processed by the processing element  62 ′, which may be programmed to generate and output signals that control operation of one or more features of the pressurization apparatus  25  to operate in the manner desired by the user. In some embodiments, the processing element  62 ′ may also receive signals from one or more sensors within the pressurization apparatus  25  or from one or more sensors associated with another component (e.g., the source conduit  23 , the inspiratory breathing conduit  29 , etc.) of the gas delivery system  20 . A processing element  62 ′ that receives such signals may be programmed to automatically operate one or more features of the pressurization apparatus  25  in such a way that one or more desired parameters (e.g, gas mix, pressure, flow rate, etc.) are substantially constantly maintained by the pressurization apparatus  25 . 
     Signals from one or more other sensors of the brain cooling system (e.g., temperature sensor  52 , etc.) may be transmitted to and/or received by a processing element  62 ′ associated with the pressurization apparatus  25 . The processing element  62 ′ may then automatically control operation of the pressurization apparatus  25  (e.g., increase or decrease the rate at which respiratory gases flow, etc.) in such a way as to provide a desired effect, such as a decrease or an increase in the temperature of the subject&#39;s brain, a change in the rate at which the subject&#39;s brain temperature increases or decreases or the like. 
     In other embodiments, a single control system may control operation of both the cooling apparatus  40  and the gas delivery system  20 , as well as any humidification component  55 , any rewarming element  57  and/or body warming element  59 . 
     A method for cooling the brain of a subject in accordance with teachings of the present invention may be useful for treating a reduction in the flow of blood into and/or through the subject&#39;s brain, or cerebral hypoperfusion. Cerebral hypoperfusion may occur during a cerebral vascular accident, such as a stroke, a traumatic brain injury, or cardiac arrest, as well as in situations where a subject may be at risk for a cerebral vascular accident or cerebral hypoperfusion, such in patients experiencing congestive heart failure, pulmonary edema, or any other condition that may slow the flow of blood into the subject&#39;s brain. Such a brain cooling method includes delivering a respiratory gas that has been cooled to a temperature below the normal body temperature (e.g., about 37° C., etc.) of a subject, to the nasal cavity of the subject. By cooling the temperature within the subject&#39;s nasal cavity, the temperature of the subject&#39;s brain may also decrease. Introduction of the cool respiratory gas into the subject&#39;s nasal cavity may selectively lower the temperature of the subject&#39;s brain without inducing general hypothermia, a technique referred to as “selective brain cooling” (SBC). Some embodiments include reducing the temperature of the subject&#39;s nasal cavity to a temperature that enables the brain to be cooled at a desired rate while limiting counterproductive vasoconstriction (e.g., to a temperature of as low as about 15° C., etc.). As a non-limiting example, such cooling may be effected by initially delivering respiratory gas at a temperature of about 2° C. into the nasal cavity. 
     Decreasing a subject&#39;s brain temperature may also reduce the subject&#39;s body temperature. In some embodiments, brain cooling may be effected while minimizing any reduction in the subject&#39;s core body temperature. For example, for each one degree centigrade (1° C.) reduction in the temperature of a subject&#39;s brain, his or her core body temperature may only decrease by 0.2° C. (i.e., the ratio of change in brain temperature to the change in core temperature is high). In other embodiments, including those where brain temperature is reduced to provide for control over the rate at which the core temperature of a subject&#39;s body is decreased, the ratio of change in brain temperature to the change in core temperature may be lower. 
     In some embodiments, a method that incorporates teachings of the present invention may rapidly cool the subject&#39;s brain. Without limiting the scope of any aspect of the present invention, a brain cooling method of the present invention may be used to decrease the temperature of a subject&#39;s brain by about 2° C. or more within about 30 minutes. In a more specific embodiment, the temperature of a subject&#39;s brain may be cooled by about 3° C. or more within about 20 minutes, or even within about 15 minutes. 
     Once a desired brain temperature (e.g., a specific temperature, such as 32° C.; a temperature within a predefined range; etc.) has been achieved, that brain temperature may be maintained or substantially maintained (e.g., vary by less than about 10%, etc.). For example, after initially administering very cold (e.g., about 2° C., etc.) respiratory gas, the temperature of the respiratory gas may be gradually increased to about 15° C. to about 20° C. 
     The cooled respiratory gas that is administered to the subject may comprise air, or it may be oxygen-rich, meaning that the gas includes a higher than normal amount of oxygen, with “normal” being the roughly 20.9%, by molar content per volume, present in air. By delivering oxygen-rich gas, the rate at which oxygen flows into the subject&#39;s blood, and thus, into the subject&#39;s brain, may be increased. 
     Respiratory gas may be administered to the nasal cavity of a subject under a positive pressure, which may exceed the normal, physiologic air pressure generated as the subject inhales spontaneously, on his or her own. By administering respiratory gas under positive pressure, the alveoli within the lungs may expand fully or almost fully, which may increase, or even optimize, the transfer of carbon dioxide out of the subject&#39;s blood and oxygen into the subject&#39;s blood and, thus, into the subject&#39;s brain. 
     In addition, respiratory gas may be administered at a flow rate that exceeds the rate at which the subject normally inhales air. An increased flow rate may increase the rate at which carbon dioxide is flushed from the subject&#39;s lungs and replaced with fresh respiratory gas. Consequently, the rate at which oxygen is exchanged for carbon dioxide in the subject&#39;s blood and in the subject&#39;s brain may be increased. Non-limiting examples of the rate at which respiratory gas may be delivered to the subject&#39;s nasal cavity include rates of about 25 liters per minute and more (e.g., 30 liters per minute, 50 liters per minute, 60 liters per minute, etc.). 
     The pressure and/or flow rate at which respiratory gas is administered may be constant or substantially constant. 
     In a study involving pigs, respiratory gas having a temperature of 2° C. was introduced into the nasal cavity under continuous positive airway pressure at a flow rate of 60 liters per minute. Brain temperature, which was monitored directly, decreased by 2° C. in eight (8) minutes and by 3° C. in 17 minutes. 
     Any of the foregoing, alone or in combination, may increase, and even optimize, the amount of oxygen with the blood of a subject, and within the subject&#39;s brain. Increasing or optimizing the amount of oxygen supplied to a subject&#39;s brain may decrease or even minimize the likelihood of damage (i.e., ischemia) or further damage to the subject&#39;s brain. 
     Systems and methods of the present invention may also be used to control (e.g., lower, etc.) the core temperature of a subject&#39;s body. As with changes in the temperature of a subject&#39;s brain, the rate of change of a subject&#39;s core temperature may be controlled, or programmed. 
     Selective brain cooling and, thus, a brain cooling process and/or body cooling process according to the present invention may continue for a prolonged period of time. For example, brain cooling may continue for an extended period of time (e.g., about an hour; up to about 48 hours or longer; about 12 hours to about 24 hours; etc.). 
     After the brain and/or body of a subject has been cooled, particularly when the brain has been cooled for a prolonged period of time, it may be desirable to increase the temperature of the brain gradually, or in a controlled manner. Accordingly, the present invention also includes methods for rewarming the brain of a subject. The manner in which a subject&#39;s brain is rewarmed, including the rate at which rewarming is effected, may be controlled in such a way as to prevent any further damage to (i.e., ischemic activity in) the subject&#39;s brain. A caregiver may program the manner in which rewarming of the brain is effected. In some embodiments, the temperature of respiratory gas introduced into a subject&#39;s nasal cavity may be gradually increased from the most recent cool temperature to a temperature at or above the normal or desired temperature of the subject&#39;s brain. 
     In specific embodiments, rewarming may be effected by introducing respiratory gas having a temperature of about 33° C. to about 39° C. into a subject&#39;s nasal cavity. Even more specifically, cooler (e.g., about 33° C. to about 35° C., etc.) respiratory gas may initially be introduced into the subject&#39;s nasal cavity, then the temperature of the respiratory gas may be gradually increased (e.g., to a temperature of about 37° C. to about 39° C., etc.). Rewarming may continue until the temperature of the subject&#39;s brain returns to normal (e.g., about 37° C.). 
     Although the foregoing description contains many specifics, these should not be construed as limiting the scope of any of the appended claims, but merely as providing information pertinent to some specific embodiments that may fall within the scopes of the appended claims. Other embodiments may also be devised which lie within the scopes of the appended claims. Features from different embodiments may be employed in combination. The scopes of the appended include all legal equivalents. All additions, deletions and modifications to the invention, as disclosed herein, that fall within the meaning and scopes of the claims are to be embraced thereby.