Patent Publication Number: US-2022226034-A1

Title: Occlusion detection using blood flow measurement

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application claims priority to Provisional Application No. 63/130,984, filed Dec. 28, 2020, which is herein incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     The present invention relates to medical devices and methods for treating cardiac arrhythmias. More specifically, the invention relates to devices and methods for applying cryotherapy to cardiac tissues. 
     BACKGROUND 
     Cardiac arrhythmias involve an abnormality in the electrical conduction of the heart and are a leading cause of stroke, heart disease, and sudden cardiac death. Treatment options for patients with arrhythmias include medications and/or the use of medical devices, which can include implantable devices and/or catheter ablation of cardiac tissue, to name a few. Catheter ablation involves delivering ablative energy to tissue inside the heart to block aberrant electrical activity from depolarizing heart muscle cells out of synchrony with the heart&#39;s normal conduction pattern. The procedure is performed by positioning the tip of an energy delivery catheter adjacent to diseased or targeted tissue in the heart. Typically, the energy delivery component of the system is at or near the most distal portion of the catheter, i.e., farthest from the user or operator, and often at the tip of the catheter. 
     Various forms of energy can be used to ablate diseased heart tissue. These can include radio frequency (RF), cryogenics, ultrasound, and laser energy, to name a few. During a cryoablation procedure, with the aid of a guide wire, the distal tip of the catheter is positioned adjacent to targeted cardiac tissue, at which time energy is delivered to create tissue necrosis, rendering the ablated tissue incapable of conducting electrical signals. 
     Atrial fibrillation (AF) is a common arrhythmia treated using catheter ablation. One AF treatment strategy involves isolating the pulmonary veins from the left atrial chamber. A particularly useful technique known as catheter balloon cryotherapy or cryoablation can be employed to treat AF. During balloon cryoablation procedures, a balloon on a balloon catheter is positioned within the ostium of the pulmonary vein to be treated and inflated to intimately contact the surrounding tissue and occlude the pulmonary vein. Traditionally, the operator will inflate the balloon with no cooling fluid provided therein, and verify occlusion using methods such as injection contrast and fluoroscopy prior to delivering the ablative, i.e., cryogenic, energy. However, using contrast agent injection to ensure pulmonary vein occlusion exposes the patient and medical personnel to radiation and requires the use of lead aprons. 
     There is a continuing need for improved systems and methods for verifying and ensuring pulmonary vein occlusion in pulmonary vein isolation procedures. 
     SUMMARY 
     Example 1 is a control system for a cryogenic ablation system. The control system includes an extracorporeal ultrasound sensor and a controller. The extracorporeal ultrasound sensor is configured to detect blood flow in a vein and generate an output signal indicative of blood flow velocity of the blood flow in the vein, and the controller is configured to receive the output signal and determine whether the vein has been occluded by a cryoablation balloon catheter. 
     In Example 2, the system of Example 1, wherein the controller is configured to determine changes in the blood flow velocity, determine average changes in the changes in the blood flow velocity during multiple time periods, and compare one or more of the average changes to a stability threshold value to determine whether the vein has been occluded. 
     In Example 3, the system of any one of Examples 1 and 2, wherein the controller determines an overall change in the blood flow velocity and compares the overall change in the blood flow velocity to an overall change threshold value to determine whether the vein has been occluded. 
     In Example 4, the system of any one of Examples 1-3, wherein the controller is an ultrasound controller and the extracorporeal ultrasound sensor is coupled to the ultrasound controller and configured to transmit and receive ultrasound frequencies through patient tissues, wherein the ultrasound controller is configured to determine the blood flow velocity. 
     In Example 5, the system of any one of Examples 1-4, wherein the controller is configured to determine the blood flow velocity based on a doppler frequency shift in the blood flow. 
     In Example 6, the system of any one of Examples 1-5, wherein the controller prevents ablation from proceeding until the controller has determined that the vein has been occluded. 
     In Example 7, the system of any one of Examples 1-6, wherein the controller provides one or more of an audio and a visual alarm in response to loss of occlusion of the vein. 
     Example 8 is a cryogenic ablation system for determining whether a pulmonary vein has been occluded. The system including a cryoablation balloon catheter, an extracorporeal ultrasound sensor, and a controller. The cryoablation balloon catheter configured to be inserted into an ostium of the pulmonary vein. The extracorporeal ultrasound sensor configured to detect blood flow in the pulmonary vein before, during, and after inflation of the cryoablation balloon catheter in the ostium of the pulmonary vein and to generate output signals indicative of blood flow velocity of the blood flow in the pulmonary vein. The controller coupled to the extracorporeal ultrasound sensor and configured to receive the output signals and determine blood flow velocity values to determine whether the pulmonary vein has been occluded by the cryoablation balloon catheter. 
     In Example 9, the system of Example 8, wherein the controller is configured to inflate the cryoablation balloon catheter in response to manually pushing an inflate control button. 
     In Example 10, the system of any one of Examples 8 and 9, wherein the controller determines at least one of average changes in changes of the blood flow velocity values during multiple time periods and an overall change in the blood flow velocity values from prior to inflation of the cryoablation balloon catheter to after inflation of the cryoablation balloon catheter. 
     In Example 11, the system of any one of Examples 8-10, further comprising a display, wherein the controller is configured to visually indicate on the display an occlusion level of the pulmonary vein. 
     In Example 12, the system of any one of Examples 8-11, further comprising a display, wherein the controller is configured to visually indicate on the display that ablation may proceed. 
     Example 13 is a method of determining a level of occlusion of a vein. The method including: inserting a cryoablation balloon catheter into an ostium of the vein; obtaining, by an ultrasound system, at least one blood flow velocity measurement of blood flow in the vein prior to inflation of the cryoablation balloon catheter; inflating the cryoablation balloon catheter in the ostium of the vein; obtaining, by the ultrasound system, multiple blood flow velocity measurements of the blood flow in the vein during inflation of the cryoablation balloon catheter; and determining, by a controller coupled to the ultrasound system and using the at least one blood flow velocity measurement and the multiple blood flow velocity measurements, the level of occlusion of the vein. 
     In Example 14, the method of Example 13, wherein determining the level of occlusion of the vein includes determining changes of blood flow velocity in the vein, determining average changes in the changes of the blood flow velocity during multiple time periods, and comparing one or more of the average changes to a threshold value. 
     In Example 15, the method of any one of Examples 13 and 14, wherein determining the level of occlusion of the vein includes determining an overall change of blood flow velocity in the vein from prior to inflation of the cryoablation balloon catheter to after inflation of the cryoablation balloon catheter and comparing the overall change of the blood flow velocity in the vein to a threshold value. 
     Example 16 is a control system for a cryogenic ablation system. The control system including an extracorporeal ultrasound sensor and a controller. The extracorporeal ultrasound sensor configured to detect blood flow in a vein and generate an output signal indicative of blood flow velocity of the blood flow in the vein, and the controller configured to receive the output signal and determine whether the vein has been occluded by a cryoablation balloon catheter. 
     In Example 17, the system of Example 16, wherein the controller is configured to determine changes in the blood flow velocity and to determine average changes in the changes in the blood flow velocity during multiple time periods to determine whether the vein has been occluded. 
     In Example 18, the system of Example 17, wherein the controller compares one or more of the average changes to a stability threshold value to determine whether the vein has been occluded. 
     In Example 19, the system of Example 16, wherein the controller determines an overall change in the blood flow velocity to determine whether the vein has been occluded. 
     In Example 20, the system of Example 19, wherein the controller compares the overall change in the blood flow velocity to an overall change threshold value to determine whether the vein has been occluded. 
     In Example 21, the system of Example 16, wherein the vein is a pulmonary vein. 
     In Example 22, the system of Example 16, wherein the controller is an ultrasound controller and the extracorporeal ultrasound sensor is coupled to the ultrasound controller and configured to transmit and receive ultrasound frequencies through patient tissues, wherein the ultrasound controller is configured to determine the blood flow velocity. 
     In Example 23, the system of Example 16, wherein the controller is configured to determine the blood flow velocity based on a doppler frequency shift in the blood flow. 
     In Example 24, the system of Example 16, wherein the controller prevents ablation from proceeding until the controller has determined that the vein has been occluded. 
     In Example 25, the system of Example 16, wherein the controller provides one or more of an audio and a visual alarm in response to loss of occlusion of the vein. 
     Example 26 is a cryogenic ablation system for determining whether a pulmonary vein has been occluded. The system including a cryoablation balloon catheter, an extracorporeal ultrasound sensor, and a controller. The cryoablation balloon catheter configured to be inserted into an ostium of the pulmonary vein. The extracorporeal ultrasound sensor configured to detect blood flow in the pulmonary vein before, during, and after inflation of the cryoablation balloon catheter in the ostium of the pulmonary vein and to generate output signals indicative of blood flow velocity of the blood flow in the pulmonary vein. The controller coupled to the extracorporeal ultrasound sensor and configured to receive the output signals and determine blood flow velocity values to determine whether the pulmonary vein has been occluded by the cryoablation balloon catheter. 
     In Example 27, the system of Example 26, wherein the controller is configured to inflate the cryoablation balloon catheter in response to manually pushing an inflate control button. 
     In Example 28, the system of Example 26, wherein the controller determines at least one of average changes in changes of the blood flow velocity values during multiple time periods and an overall change in the blood flow velocity values from prior to inflation of the cryoablation balloon catheter to after inflation of the cryoablation balloon catheter. 
     In Example 29, the system of Example 26, further comprising a display, wherein the controller is configured to visually indicate on the display an occlusion level of the pulmonary vein. 
     In Example 30, the system of Example 26, further comprising a display, wherein the controller is configured to visually indicate on the display that ablation may proceed. 
     Example 31 is a method of determining a level of occlusion of a vein. The method including: inserting a cryoablation balloon catheter into an ostium of the vein; obtaining, by an ultrasound system, at least one blood flow velocity measurement of blood flow in the vein prior to inflation of the cryoablation balloon catheter; inflating the cryoablation balloon catheter in the ostium of the vein; obtaining, by the ultrasound system, multiple blood flow velocity measurements of the blood flow in the vein during inflation of the cryoablation balloon catheter; and determining, by a controller coupled to the ultrasound system and using the at least one blood flow velocity measurement and the multiple blood flow velocity measurements, the level of occlusion of the vein. 
     In Example 32, the method of Example 31, wherein determining the level of occlusion of the vein includes determining changes of blood flow velocity in the vein and determining average changes in the changes of the blood flow velocity during multiple time periods. 
     In Example 33, the method of Example 32, wherein determining the level of occlusion of the vein includes comparing one or more of the average changes to a threshold value. 
     In Example 34, the method of Example 31, wherein determining the level of occlusion of the vein includes determining an overall change of blood flow velocity in the vein from prior to inflation of the cryoablation balloon catheter to after inflation of the cryoablation balloon catheter. 
     In Example 35, the method of Example 34, wherein determining the level of occlusion of the vein includes comparing the overall change of the blood flow velocity in the vein to a threshold value. 
     While multiple embodiments are disclosed, still other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a simplified schematic side view illustration of a patient and a cryogenic balloon catheter system, according to embodiments of the disclosure; 
         FIG. 2A  is a simplified schematic view illustration of a portion of the patient and a portion of the cryogenic balloon catheter system with an expandable balloon that is partially inflated or deflated in the pulmonary vein and blood flow in the pulmonary vein and past the expandable balloon, according to embodiments of the disclosure. 
         FIG. 2B  is a simplified schematic view illustration of a portion of the patient and a portion of the cryogenic balloon catheter system with the expandable balloon inflated to occlude the pulmonary vein, such that blood flow past the expandable balloon is prevented, according to embodiments of the disclosure. 
         FIG. 3A  is a diagram illustrating the graphical display including an occlusion level indicator prior to reaching a satisfactory level of occlusion for ablation to proceed, according to embodiments of the disclosure. 
         FIG. 3B  is a diagram illustrating the graphical display including the occlusion level indicator and an ablation button, after reaching a level of occlusion where ablation may proceed, according to embodiments of the disclosure. 
         FIG. 4  is a flow chart diagram illustrating a method of determining a level of occlusion of a vein and/or whether the vein has been occluded, according to embodiments of the disclosure. 
     
    
    
     While the disclosure is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the disclosure to the particular embodiments described. On the contrary, the disclosure is intended to cover all modifications, equivalents, and alternatives falling within the scope of the disclosure as defined by the appended claims. 
     DETAILED DESCRIPTION 
       FIG. 1  is a simplified schematic side view illustration of a cryogenic balloon catheter system  10  for use with a patient  12 , which can be a human being or an animal, according to embodiments of the disclosure. Although the design of the cryogenic balloon catheter system  10  can be varied depending on the particular clinical needs of the patient  12 , in the illustrated example the cryogenic balloon catheter system  10  includes one or more of a balloon catheter  14 , an extracorporeal ultrasound system  16 , a control console  22 , a graphical display  24 , and a fluid control system  28 . Also, although  FIG. 1  illustrates the structures of the cryogenic balloon catheter system  10  in a specific position, sequence and/or order, in other examples, these structures can be in different positions, sequences, and/or order than that illustrated in  FIG. 1 . In addition, the cryogenic balloon catheter system  10  can include fewer or additional components than those specifically illustrated and described herein. 
     The cryogenic balloon catheter system  10  is configured to improve vein occlusion in vein isolation procedures, such as in pulmonary vein isolation procedures, by improving verification of vein occlusion in these procedures. In the cryogenic balloon catheter system  10 , the extracorporeal ultrasound system  16  is used to monitor blood flow through a vein of interest to determine whether blood flow through the vein has been stopped or substantially stopped, such that the vein has been occluded and ablation can proceed. 
     The extracorporeal ultrasound system  16  includes an extracorporeal ultrasound transducer or sensor  18  and an ultrasound control system  20  that is illustrated in phantom and disposed within the control console  22 . The extracorporeal ultrasound transducer  18  is electrically and communicatively coupled to the ultrasound control system  20  by conductive path  26 . The ultrasound control system  20  includes a controller  32 , such as a microprocessor, and memory storing code that is executable by the controller  32  to perform functions of the cryogenic balloon catheter system  10 . Also, in embodiments, the control console  22  includes a controller  34 , such as a microprocessor, and memory storing code that is executable by the controller  34  to perform functions of the cryogenic balloon catheter system  10 . 
     In embodiments, the ultrasound control system  20  determines the velocity of blood flowing through the vein of interest, such as a pulmonary vein, from signals received by the ultrasound control system  20  from the extracorporeal ultrasound transducer  18 . The extracorporeal ultrasound transducer or sensor  18  is configured to detect blood flow through the vein and generate an output signal indicative of blood flow velocity of the blood flow through the vein. The controller  32  of the ultrasound control system  20  is configured to receive the output signal and determine the velocity of the blood flow in the vein. Using these velocity measurements, the controller  32  of the ultrasound control system  20  or the controller  38  of the control console  22  determines whether the vein has been occluded, such as by a cryoablation balloon catheter. In embodiments, the controller  32  of the ultrasound control system  20  or the controller  38  of the control console  22  determines the degree or level of occlusion of the vein and whether ablation may proceed. Also, in embodiments, the controller  38  of the control console  22  can be configured to receive the output signal and determine the velocity of the blood flow in the vein. 
     The ultrasound control system  20  and/or the control console  22  are communicatively coupled to the graphical display  24 , which can include a graphical user interface (GUI), to display at least one of whether the vein has been occluded, the degree or level of occlusion of the vein, and whether ablation may proceed. 
     In further description of the cryogenic balloon catheter system  10 , the balloon catheter  14  includes a handle assembly  40 , and a shaft  44  having a proximal end portion  48  connected to the handle assembly  40 , and a distal end portion  52 , shown disposed within the patient  12 . As will be appreciated, the handle assembly  40  can include various components, such as a control element  58 , that the user can manipulate to operate the balloon catheter  14 . Also, an umbilical  60  operatively connects the handle assembly  40  and the active components of the balloon catheter  14  to the control console  22 . In embodiments, the system  10  may include additional components or alternative approaches to operatively connect the balloon catheter  14  to the control console  22 . 
     The fluid control system  28  includes a fluid source  30  and a fluid control arrangement  34 , which are illustrated in phantom and disposed within the control console  22 . In embodiments, the fluid control system  28  can include various conduits, valves and instrumentation configured to supply and withdraw a fluid to the active elements on the balloon catheter  14 . The fluid source  30  is operably connected to the fluid control arrangement  34  by a conduit  36 , which may be in the form of a hose or tubing, configured to transfer fluid contained within the fluid source  30  to components making up the fluid control arrangement  34 . 
     The fluid control system  28  includes a controller  42 , such as a microprocessor, and memory storing code that is executable by the controller  42  to perform the functions of the fluid control system  28 . In embodiments, the fluid control system  28  is configured to monitor and control various processes of the ablation procedures performed with the cryogenic balloon catheter system  10 . More specifically, the fluid control system  28  can monitor and control release and/or retrieval of a cooling fluid  68 , e.g., a cryogenic fluid, shown schematically contained within the fluid source  30 , to the balloon catheter  14 , e.g., via fluid injection and fluid exhaust lines (not shown), but which may be disposed within the umbilical  60 . The fluid control system  28  can also control various structures that are responsible for maintaining and/or adjusting a flow rate and/or pressure of the cryogenic fluid  68  that is released to the balloon catheter  14  during the cryoablation procedure. In embodiments, the cryogenic balloon catheter system  10  delivers ablative energy in the form of cryogenic fluid  68  to cardiac tissue of the patient  12  to create tissue necrosis, rendering the ablated tissue incapable of conducting electrical signals. Additionally, in embodiments, the fluid control system  28  can control activation and/or deactivation of one or more other processes of the balloon catheter  14 . 
     Further, or in the alternative, the fluid control system  28  can receive data and/or other information, hereinafter sometimes referred to as sensor output, from various structures within the cryogenic balloon catheter system  10 . In some embodiments, the fluid control system  28  can receive, monitor, assimilate and/or integrate the sensor output, and/or any other data or information received from any structure within the cryogenic balloon catheter system  10  in order to control the operation of the balloon catheter  14 . Also, in embodiments, the fluid control system  28  can initiate and/or terminate the flow of cryogenic fluid  68  to the balloon catheter  14  based on the sensor output. 
     As shown in  FIG. 1 , in embodiments, the fluid control system  28  can be positioned substantially within the control console  22 . Alternatively, at least a portion of the fluid control system  28  can be positioned in one or more other locations within the cryogenic balloon catheter system  10 , e.g., within the handle assembly  40 . 
     The fluid source  16  contains the cryogenic fluid  68 , which is delivered to and from the balloon catheter  14  with or without input from the fluid control system  28  during a cryoablation procedure. Once the ablation procedure has initiated, the cryogenic fluid  68  can be delivered and the resulting gas, after a phase change, can be retrieved from the balloon catheter  14 , and can either be vented or otherwise discarded as exhaust. Additionally, the type of cryogenic fluid  68  that is used during the cryoablation procedure can vary. In some embodiments, the cryogenic fluid  68  can include liquid nitrous oxide. However, any other suitable cryogenic fluid  68  can be used. For example, in some embodiments, the cryogenic fluid  68  can include liquid nitrogen. 
     The design of the balloon catheter  14  can be varied to suit the specific design requirements of the cryogenic balloon catheter system  10 . As shown, the balloon catheter  14  is inserted into the body of the patient  12  during the cryoablation procedure. The handle assembly  40  can be handled and used by the operator to operate, position and control the balloon catheter  14 . The design and specific features of the handle assembly  40  can vary to suit the design requirements of the cryogenic balloon catheter system  10 . In embodiments, the handle assembly  40  is separate from, but in electrical and/or fluid communication with the fluid control system  28 , the fluid source  16 , and the graphical display  24 . In some embodiments, the handle assembly  40  can integrate and/or include at least a portion of the fluid control system  28  within an interior of the handle assembly  40 . Also, it is understood that the handle assembly  40  can include fewer or additional components than those specifically illustrated and described herein and, in some embodiments, the handle assembly  40  can include circuitry (not shown in  FIG. 1 ) that can include at least a portion of the fluid control system  28 . For example, the circuitry can transmit electrical signals such as the sensor output, or otherwise provide data to the fluid control system  28 . In embodiments, the circuitry can include a printed circuit board having one or more integrated circuits and/or other circuits. In some embodiments, the handle assembly  40  can be used by the operator to initiate and/or terminate the cryoablation process, e.g., to start the flow of the cryogenic fluid  68  to the balloon catheter  14  in order to ablate certain targeted heart tissue of the patient  12 . 
     In embodiments, the control console  22  includes at least a portion of the extracorporeal ultrasound system  16 , the fluid control system  28 , the fluid source  30 , and the graphical display  24 . Also, in embodiments, the control console  22  can contain additional structures not shown or described herein or the control console  22  may not include structures that are illustrated within the control console  22  in  FIG. 1 . For example, in embodiments, the control console  22  does not include the graphical display  24 . 
     During cryoablation procedures, the balloon catheter  14  and the control console  22  are operatively connected to allow the flow of cryogenic fluid  68  from the control console  22  to the balloon catheter  14  and back to the control console  22 . Generally, during the application of ablative energy, the cryogenic fluid  68  flows in a liquid phase to the balloon catheter  14 , where the cryogenic fluid  68  undergoes a phase change and returns to the control console  22  as exhaust in a gaseous phase. 
     In embodiments, the graphical display  24  is electrically connected to one or more of the fluid control system  28 , the control console  22 , and the ultrasound control system  20 . Additionally, the graphical display  24  provides the operator of the cryogenic balloon catheter system  10  with information that can be used before, during, and after the cryoablation procedure. For example, the graphical display  24  can provide the operator with information based on the sensor output, and any other relevant information that can be used before, during, and after the cryoablation procedure. The specifics of the graphical display  24  can vary depending upon the design requirements of the cryogenic balloon catheter system  10 , and the specific needs, specifications, and/or desires of the operator. 
     In embodiments, the graphical display  24  can provide static visual data and/or information to the operator via various frames or other representations  70 . In addition, the graphical display  24  can provide dynamic visual data and/or information to the operator, such as video data or any other data that changes over time, e.g., during an ablation procedure. Further, in embodiments, the graphical display  24  can include one or more colors, different display sizes, varying brightness, etc., that may act as alerts to the operator. Also, in embodiments, the graphical display  24  can provide audio data or information to the operator. In embodiments, the graphical display  24  includes a GUI. 
     In operation of the cryogenic balloon catheter system  10 , the balloon catheter  14  is inserted into the vein of interest, such as into an ostium of the vein of interest, in the patient  12  and the extracorporeal ultrasound system  16  is used to obtain one or more blood flow velocity measurements or values of the blood flow in the vein. Next, the cryoablation balloon catheter  14  is inflated to occlude the vein, reducing and preventing blood flow in or through the vein, and the extracorporeal ultrasound system  16  is used again to obtain more blood flow velocity values of the blood flow through the vein during inflation of the balloon catheter  14  and after inflation of the balloon catheter  14 . Based on the obtained blood flow velocity values, the cryogenic balloon catheter system  10  determines one or more of whether the vein is occluded, the degree or level of occlusion of the vein, and whether the cryogenic balloon catheter system  10  may proceed with ablation. In embodiments, if the level of occlusion of the vein does not meet a threshold level of occlusion, the cryogenic balloon catheter system  10  locks the system  10 , preventing the system  10  from providing ablation. In embodiments, if occlusion has been achieved and then lost during a vein isolation procedure, the cryogenic balloon catheter system  10 , such as the control console  22 , sets off an alarm to alert the user, where the alarm may be a visual and/or audio alarm provided via the graphical display  24 . 
     In embodiments, each of the blood flow velocity measurements is determined by the control console  22  or the ultrasound control system  20 . In embodiments, the velocity V of the blood flowing in or through the vein is determined using a doppler ultrasound measurement technique and the following Formula 1: 
     
       
         
           
             
               
                 
                   
                     f 
                     d 
                   
                   = 
                   
                     
                       2 
                       ⁢ 
                       
                         ( 
                         
                           
                             f 
                             c 
                           
                           × 
                           cos 
                           ⁢ 
                           θ 
                           × 
                           V 
                         
                         ) 
                       
                     
                     c 
                   
                 
               
               
                 
                   Formula 
                   ⁢ 
                   
                       
                   
                   ⁢ 
                   1 
                 
               
             
           
         
       
     
     where, fd is the doppler frequency, V is the velocity of the blood in the vein, theta is the angle between the transducer and the vein, c is the speed of sound moving through soft tissues, which is approximately 1.5×10{circumflex over ( )}5 centimeters/second, and fc is the transmitted frequency. 
     The cryogenic balloon catheter system  10  then determines whether the vein has been occluded, the degree or level of occlusion of the vein, and/or whether ablation may proceed based on the multiple velocity measurements, as described below in relation to  FIGS. 2A and 2B . 
       FIGS. 2A and 2B  are diagrams illustrating the balloon catheter  14  partially inflated or deflated in a pulmonary vein  108  and the balloon catheter  14  inflated to occlude the pulmonary vein  108 , according to embodiments of the disclosure. 
     More specifically,  FIG. 2A  is a simplified schematic view illustration of a portion of the patient  12  and a portion of the cryogenic balloon catheter system  10  with an expandable balloon  110  that is partially inflated or deflated in the pulmonary vein  108  and blood flow  102  through the pulmonary vein  108  and past the expandable balloon  110 , according to embodiments of the disclosure.  FIG. 2B  is a simplified schematic view illustration of a portion of the patient  12  and a portion of the cryogenic balloon catheter system  10  with the expandable balloon  110  inflated to occlude the pulmonary vein  108 , such that blood flow  102  past the expandable balloon  100  is prevented, according to embodiments of the disclosure. 
       FIGS. 2A and 2B  are schematic illustrations of the distal end portion  52  of the balloon catheter  14  positioned within a selected anatomical region of the patient  12 , in this case, a left atrium  100  adjacent to an ostium  104  of a pulmonary vein  108 , such as when the system  10  is used in a pulmonary vein isolation (PVI) procedure to terminate an atrial fibrillation. The balloon catheter  14  includes the expandable balloon  110 , a guidewire lumen  114  and an injection tube  118 . As shown, the balloon  110  has a proximal end  130  and an opposite distal end  134  and defines an internal space  138  that creates a cryo-chamber during a cryoablation procedure. In embodiments, the proximal end  130  of the balloon  110  is attached to the distal end portion  52  of the shaft  44 , and the distal end  134  of the balloon  110  is attached to the guidewire lumen  114  near the distal end thereof. Also, in embodiments, the injection tube  118  is disposed within and extends from the shaft  44 , and terminates within and is open to the internal space  138 . The injection tube  118  is operable to deliver the cryogenic fluid  68  to the internal space  138 . 
     Although not shown in  FIGS. 2A and 2B , the balloon catheter  14  also includes an exhaust lumen within the shaft  44  and open to the internal space  138 . The exhaust lumen is operable to facilitate evacuation of the cryogenic fluid  68  from the internal space  138  and to facilitate inflation of the balloon  110 . In embodiments, the guidewire lumen  114  may be slidable relative to the shaft  44  to facilitate expansion and subsequent collapse of the balloon  110  in use. 
     As illustrated, an instrument  144  is shown extending through and beyond the guidewire lumen and into the pulmonary vein  108 . As the skilled artisan will appreciate, the instrument  144  may be a guidewire, mapping wire or catheter, anchoring wire, or other medical device useful to facilitate the a cryo-therapy procedure. However, the use of the instrument  144  is optional. 
     In the embodiments of  FIGS. 2A and 2B , the balloon  110  is a dual-balloon construction including an inner balloon  150  and an outer balloon  154 . The balloons  150  and  154  are configured such that the inner balloon  150  receives the cryogenic fluid  68  and the outer balloon  154  surrounds the inner balloon  150 . The outer balloon  154  acts as part of a safety system to capture the cryogenic fluid  68  in the event of a leak from the inner balloon  150 . It is understood that the balloon catheter  14  can include other structures as well. However, for the sake of clarity, these other structures have been omitted from the figures. Additionally, it is further appreciated that in some alternative embodiments, the balloon catheter  14  includes only a single balloon. 
     The balloon catheter  14  is positioned within the left atrium  100  of the patient  12 . The guidewire  144  and guidewire lumen  114  are inserted into a pulmonary vein  108  of the patient  12 , and the catheter shaft  44  and the balloons  150  and  154  are moved along the guidewire  144  and/or the guidewire lumen  114  to be positioned near the ostium  104  of the pulmonary vein  108 . 
     During use, the inner balloon  150  can be partially or fully inflated so that at least a portion of the inner balloon  150  expands against at least a portion of the outer balloon  154 . Once the inner balloon  150  is sufficiently inflated, an outer surface of the outer balloon  154  can then be positioned to abut and/or substantially form a seal with the ostium  104  of the pulmonary vein  108  to be treated. 
     The inner balloon  150  and the outer balloon  154  can be formed from any suitable materials. For example, in some embodiments, the inner balloon  150  can be formed from a sturdy material to better inhibit leaks of the cryogenic fluid  68  that is received therein, and the outer balloon  154  can be made from a relatively compliant material to ensure better contact and positioning between the outer balloon  154  and the pulmonary vein  108 . 
     During balloon cryoablation procedures, prior to delivering the cryo-ablative energy, the operator can inflate the balloon  110  using the cryogenic fluid  68  at a relatively high temperature, i.e., above the temperature used to ablate the target tissue. In this way, the operator can achieve balloon-tissue contact and vein occlusion to increase probability of vein isolation before starting the ablation. In addition, to minimize procedure time, it can be desirable to utilize the exhaust lumen of the balloon catheter  14  as a conduit for delivering the cryogenic fluid  68  to the internal space  138  during the inflation phase, i.e., due to its relatively large size compared to the injection tube  118 . It is also desirable to maintain relatively close control over the inflation pressure during the cryoablation procedure. For example, a drop in the inflation pressure can result in partial deflation of the balloon  110  and consequent or diminishment of balloon-tissue contact and vessel occlusion. 
     As will be appreciated, proper vein occlusion is an important factor in accomplishing pulmonary vein isolation via cryoablation. In particular, inadequate occlusion can result in blood flow past the surface of the balloon  110 , reducing the efficiency of heat transfer between the target tissue and the balloon  110 , which in turn can increase ablation procedure time or, in some cases, inhibit the formation of an ablation lesion capable of creating the desired conduction block. To verify vein occlusion and achieve good vein occlusion, the cryogenic balloon catheter system  10  determines whether the vein has been occluded, the degree or level of occlusion of the vein, and/or whether ablation may proceed, based on multiple velocity measurements of the blood flow  102 . 
     In embodiments, the cryogenic balloon catheter system  10  determines the overall change in velocity of the blood flow  102  in the vein  108  from before inflation of the balloon  110  to after inflation of the balloon  110 . In embodiments, the cryogenic balloon catheter system  10  determines changes in velocity of the blood flow  102  during inflation of the balloon  110 . 
     In embodiments, V 0  is the velocity of the blood flow  102  in the pulmonary vein  108  before inflation of the balloon  110  in the pulmonary vein  108 , such as depicted in  FIG. 2A , V n  is the velocity of the blood flow  102  in the pulmonary vein  108  after inflation of the balloon  110  in the pulmonary vein  108 , such as depicted in  FIG. 2B , and the change of velocity is given by the following Formula 2: 
       Δ V=V   0   −V   n    Formula 2
 
     where, if there is good occlusion of the pulmonary vein  108 , V n ≈0, and ΔV is higher and closer to the value of V 0 . 
     In another aspect, the cryogenic balloon catheter system  10  monitors the change in the velocity ΔV and stabilization of the change in the velocity ΔV over time. In embodiments, the cryogenic balloon catheter system  10  determines the velocity or speed of the blood flow  102  in the pulmonary vein  108  on a periodic basis, such as once every 40 milliseconds (ms), and calculates the change in the velocity ΔV for each sample. Over a longer periodic interval, such as 2 seconds, the samples of the changes in the velocity ΔV are averaged to obtain an average change in velocity over the longer periodic interval. The average change of the change in velocity values can be monitored over time to determine whether the vein, such as the pulmonary vein  108 , has been occluded, the degree or level of occlusion of the vein, and/or whether ablation may proceed 
     For example, determining the velocity every 40 ms over a 2 second interval results in 50 samples of the change in velocity taken over the 2 second interval. These 50 samples are averaged to provide an average change in velocity value over the 2 second interval, as indicated in the following Formula 3: 
     
       
         
           
             
               
                 
                   
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     Better occlusion is indicated where: ΔV approaches V 0 , which means V n ≈0; and Δ average  is zero or approaches zero. In embodiments, ΔV is compared to a corresponding threshold value, which may be determined using V 0  or a percentage of V 0 , and the level of occlusion is determined and/or a go/no-go indication is provided for the ablation procedure. In embodiments, Δ average  is compared to a corresponding stability threshold value and the degree of occlusion is determined or a go/no-go indication is provided for the ablation procedure. 
       FIGS. 3A and 3B  are diagrams illustrating the graphical display  24  during an ablation procedure including a vein isolation procedure, according to embodiments of the disclosure. 
       FIG. 3A  is a diagram illustrating the graphical display  24  including an occlusion level indicator  200  prior to reaching a satisfactory level of occlusion for ablation to proceed, according to embodiments of the disclosure. The occlusion level indicator  200  is a dynamic level indicator that changes over time during the ablation and the vein isolation procedure. Also, the graphical display  24  includes various frames and other representations  70  to provide static and dynamic visual data and information to the operator. 
     In embodiments, as the balloon  110  is inflated in the pulmonary vein  108 , the occlusion level indicated in the occlusion level indicator  200  increases from a smaller bar width to a larger bar width corresponding to increases in the overall change in the velocity of the blood flow ΔV and decreases in the Δ average . In embodiments, the occlusion level indicator  200  indicates the level of occlusion in color, such as red to yellow bar widths prior to reaching a satisfactory level of occlusion for ablation to proceed and green bar widths after reaching a level of occlusion where ablation may proceed. 
       FIG. 3B  is a diagram illustrating the graphical display  24  including the occlusion level indicator  200  and an ablation button  202  after reaching a level of occlusion where ablation may proceed, according to embodiments of the disclosure. The occlusion level indicator  200  turns green and the ablation button  202  lights up, i.e., is displayed, after reaching the level of occlusion where ablation may proceed. In embodiments, the level of occlusion where ablation may proceed is determined using one or more threshold values for the overall change in the velocity of the blood flow ΔV and the Δ average  levels. 
       FIG. 4  is a flow chart diagram illustrating a method of determining a level of occlusion of a vein and/or whether the vein has been occluded, according to embodiments of the disclosure. 
     At  300 , the method includes inserting a cryoablation balloon catheter into a vein. In embodiments, this includes inserting a cryoablation balloon catheter, such as cryoablation balloon catheter  14 , into a vein, such as the pulmonary vein  108 . Also, in some embodiments, this includes inserting a cryoablation balloon catheter into an ostium of the vein. 
     Next, at  302 , the method includes obtaining, by an ultrasound system, at least one blood flow velocity measurement of blood flow in the vein prior to inflation of the cryoablation balloon catheter. In embodiments, this includes obtaining a measure of V 0  which is the velocity of the blood flow  102  in the pulmonary vein  108  before inflation of the balloon  110  in the pulmonary vein  108 , such as depicted in  FIG. 2A . 
     At  304 , the method includes inflating the cryoablation balloon catheter in the vein. Which, in embodiments, includes inflating the cryoablation balloon catheter  14  in the ostium  104  of the pulmonary vein  108 , such as depicted in  FIG. 2B . 
     At  306 , the method includes obtaining, by the ultrasound system, multiple blood flow velocity measurements of the blood flow in the vein during inflation of the cryoablation balloon catheter. 
     And, at  308  the method includes determining, by a controller coupled to the ultrasound system and using the at least one blood flow velocity measurement and the multiple blood flow velocity measurements, the level of occlusion of the vein and/or whether the vein has been occluded. 
     In embodiments, determining the level of occlusion of the vein includes determining changes of blood flow velocity in the vein and determining average changes in the changes of the blood flow velocity during multiple time periods. Also, in embodiments, determining the level of occlusion of the vein includes comparing one or more of the average changes to a threshold value, such as a stability threshold value. 
     In addition, in embodiments, determining the level of occlusion of the vein includes determining an overall change of blood flow velocity in the vein from prior to inflation of the cryoablation balloon catheter to after inflation of the cryoablation balloon catheter and, in embodiments, comparing the overall change of the blood flow velocity in the vein to an overall threshold value. 
     Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present disclosure. For example, while the embodiments described above refer to particular features, the scope of this disclosure also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present disclosure is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.