Patent Publication Number: US-6990370-B1

Title: Method for mapping heart electrophysiology

Description:
CROSS REFERENCED TO RELATED CASES 
     This application is a continuation of Ser. No. 09/005,105, filed Jan. 9, 1998, now abandoned, which is a continuation-in-part of Ser. No. 08/387,832, filed May 26, 1995, now U.S. Pat. No. 6,240,307, which is a national stage application of PCT/US93/09015, filed Sep. 23, 1993, which in turn claims priority from U.S. Ser. No. 07/950,448, filed Sep. 23, 1992, now U.S. Pat. No. 5,297,549 and U.S. Ser. No. 07/949,690, filed September 23, 1992, now U.S. Pat. No. 5,311,866. 
    
    
     FIELD OF THE INVENTION 
     The parent invention relates to electrophysiology apparatus which is used to measure and to visualize electrical activity occurring in a patient&#39;s heart. The system can display both a visual map of the underlying electrical activity originating in a chamber of a patient&#39;s heart and the location of a therapy catheter located within a heart chamber. The electrophysiology apparatus includes several subsystems including: a therapy catheter system, a measurement catheter system and a computer based signal acquisition, control and display system. 
     BACKROUND OF THE INVENTION 
     Many cardiac tachyarrhythmias are caused by conduction defects which interfere with the normal propagation of electrical signals in a patient&#39;s heart. These arrhythmias may be treated electrically, pharmacologically or surgically. The optimal therapeutic approach to treat a particular tachyarrhythmia depends upon the nature and location of the underlying conduction defect. For this reason electrophysiologic mapping is used to explore the electrical activity of the heart during a tachyarrhythmic episode. The typical electrophysiologic mapping procedure involves positioning an electrode system within the heart. Electrical measurements are made which reveal the electrical propagation of activity in the heart. If ablation is the indicated therapy then a therapy catheter is positioned at the desired location within the heart and energy is delivered to the therapy catheter to ablate the tissue. 
     There are numerous problems associated with these electrophysidlogic diagnostic and therapeutic procedures. First the testing goes on within a beating heart. The motion of the diagnostic catheter and treatment catheter can injure the heart and provoke bouts of arrhythmia which interfere with the collection of diagnostic information. During the delivery of ablation therapy it is common to use fluoroscopic equipment to visualize the location of the catheters. Many physicians are concerned about routine occupational exposure to X-rays. In addition, the traditional mapping techniques do not provide a high resolution view of the electrical activity of the heart which makes it difficult to precisely locate the source of the arrhythmia. 
     SUMMARY 
     The electrophysiology apparatus of the invention is partitioned into several interconnected subsystems. The measurement catheter system introduces a modulated electric field into the heart chamber. The blood volume and the moving heart wall surface modify the applied electric field. Electrode sites within the heart chamber passively monitor the modifications to the field and a dynamic representation of the location of the interior wall of the heart is developed for display to the physician. Electrophysiologic signals generated by the heart itself are also measured at electrode sites within the heart and these signals are low pass filtered and displayed along with the dynamic wall representation. This composite dynamic electrophysiologic map may be displayed and used to diagnose the underlying arrhythmia. 
     A therapy catheter system can also be introduced into the heart chamber. A modulated electrical field delivered to an electrode on this therapy catheter can be used to show the location of the therapy catheter within the heart. The therapy catheter location can be displayed on the dynamic electrophysiologic map in real time along with the other diagnostic information. Thus the therapy catheter location can be displayed along with the intrinsic or provoked electrical activity of the heart to show the relative position of the therapy catheter tip to the electrical activity originating within the heart itself. Consequently the dynamic electrophysiology map can be used by the physician to guide the therapy catheter to any desired location within the heart. 
     The dynamic electrophysiologic map is produced in a step-wise process. First, the interior shape of the heart is determined. This information is derived from a sequence of geometric measurements related to the modulation of the applied electric field. Knowledge of the dynamic shape of the heart is used to generate a representation of the interior surface of the heart. 
     Next, the intrinsic electrical activity of the heart is measured. The signals of physiologic origin are passively detected and processed such that the magnitude of the potentials on the wall surface may be displayed on the wall surface representation. The measured electrical activity may be displayed on the wall surface representation in any of a variety of formats. Finally, a location current may be delivered to a therapy catheter within the same chamber. The potential sensed from this current may be processed to determine the relative or absolute location of the therapy catheter within the chamber. 
     These various processes can occur sequentially or simultaneously several hundred times a second to give a continuous image of heart activity and the location of the therapy device. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       An exemplary and illustrative form of the invention is shown in the drawings and identical reference numerals refer to equivalent structure throughout. 
         FIG. 1  is a schematic block diagram of the electrophysiology apparatus; 
         FIG. 2  is a block diagram representing the partitioning of the electrophysiology apparatus; 
         FIG. 3  is a diagram of an illustrative balloon electrode set implementation of the measurement catheter and a therapy catheter; 
         FIG. 4  is a schematic diagram of an illustrative basket electrode set implementation of the measurement catheter; 
         FIG. 5  is a flow chart showing the wall surface generation process; 
         FIG. 6  is a schematic diagram of a row of electrodes of the balloon catheter and their use in measuring distance to the heart chamber wall; 
         FIG. 7  is a screen display representing the motion of the cardiac wall surface; 
         FIG. 8  is a schematic block diagram of the portion of the electrophysiology apparatus which implements the body orientation generation process; 
         FIG. 9  is a flow charting showing the body orientation generation process; 
         FIG. 10  is a flow chart showing the wall electrogram generation process; 
         FIG. 11  is a representative screen display showing wall electrogram information; 
         FIG. 12  is a representative screen display showing wall electrogram information; 
         FIG. 13  is a representative screen display showing wall electrogram information; 
         FIG. 14  is a flow chart showing the site electrogram generation process; and 
         FIG. 15  is a flow chart showing the movable electrode location process. 
         FIG. 16  is a schematic block diagram of the therapy catheter system; 
         FIG. 17  is a schematic diagram of the laser delivery embodiment of the therapy catheter; 
         FIG. 18  is a schematic diagram of a microwave delivery embodiment of the therapy catheter; 
         FIG. 19  is a schematic diagram of a chemical delivery embodiment of the therapy catheter; and 
         FIG. 20  is a schematic diagram of the angioplasty catheter embodiment of the therapy catheter. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  shows the electrophysiologic apparatus  10  connected to a patient  12 . In a typical procedure a monitoring catheter system  14  is placed in the heart  16  to generate a display of the electrical activity of the heart  16 . After diagnosis a therapy catheter  18  may be inserted into the heart to perform ablation or other corrective treatment. 
     The monitoring catheter  14  has a proximal end  20  which may be manipulated by the attending physician, and a distal end  22  which carries a monitoring catheter electrode set  44 . In general the distal end  22  of the monitoring catheter  14  will be relatively small and will float freely in the heart chamber. The therapy catheter  18  has a distal end  24  which carries a therapy catheter electrode set  46 . The therapy catheter also has proximal end  26  which can be manipulated by the attending physician. 
     The electrode sets located on the catheters are coupled to an interface system  28 , through appropriate cables. The cable  30  connects the monitoring catheter electrode set  44  to the interface system  28  while cable  32  connects the therapy catheter electrode set  46  to the interface system  28 . The interface system  28  contains a number of subsystems which are controlled by a computer  34 . The data collected by the interface system  28  is manipulated by the computer  34  and displayed on a display device  36 . Surface electrodes represented by electrode  40  may also be coupled to the electrophysiology apparatus  10  for several purposes via an appropriate cable  42 . A therapy generator  38  is connected to the therapy catheter electrode  60  and to the therapy surface ground  70 , through the interface system  28 . The skin surface electrode cable  42  couples the ECG surface electrodes  74  to the ECG system  39 , which may be a subsystem of interface system  28 . 
       FIG. 2  is a schematic diagram showing an illustrative segmentation of the electrode sets and their electrical connections to subsystems in the electrophysiology apparatus  10 . For example the monitoring electrode set  44  contains a subset of passive electrodes  48  which are connected to a signal conditioner  50 . The monitoring electrode set  44  also contains a subset of active electrodes  52  which are connected to a signal generator  54  through a switch  59 . The signal generator  54  is controlled by the computer  34 . In operation, the signal generator  54  generates a burst of (4800 Hz for example) signals which are supplied to the active electrode set  52 . This energy sets up an electric field within the heart  16  chamber. The electrical potentials present on the passive electrode set  48  represent the summation of the underlying electrophysiological signals generated by the heart and the field induced by the burst. The signal conditioner  50  separates these two components. The preferred technique is to separate the signals based upon their frequency. 
     The high pass section  56  of the signal conditioner extracts the induced field signals as modulated by the blood volume and the changing position of the chamber walls  125 . First, the signals are amplified with a gain of approximately  500  from passive electrodes  48  with amplifier  151 . Next, the signals are high pass filtered at roughly 1200 Hz by filter  153 . Then the 4800 Hz signal is extracted by demodulator  155 . Finally, the individual signals are converted to digital format by the analog to digital converter  157  before being sent to the computer  34 . 
     The low pass section  58  of the signal conditioner  50  extracts physiologic signals. First, signal drift is reduced with a 0.01 Hz high pass filter  143 . Next, a programmable gain amplifier  145  amplifies the signals. Then a low pass filter  147  removes extraneous high frequency noise and the signal from the induced field. Finally, the physiologic signals are converted to digital format by the analog to digital converter  149  before being sent to the computer  34 . 
     The therapy catheter electrode set  46  includes at least one therapy delivery electrode  60 , and preferably one or more monitoring electrodes  62 , and one or more locator electrodes  68 . The therapy delivery electrode  60  cooperates with the ground electrode  70 , which is generally a skin patch electrode, to deliver ablation energy to the heart. These electrodes are coupled to the ablation energy generator  38  which is shown as an RF current source. A locator electrode  68  is provided which is preferably proximate the delivery electrode  60 , but can be a separate electrode site located near the distal end  24  of the therapy catheter  18 . This electrode site is coupled with an active electrode  52  through a switch  59  to the signal generator  54 . In use, the electric field coupled to the therapy catheter  18  permits the physician to track and visualize the location of the locator electrode  68  on the display device  36 . The therapy catheter electrode set  46  can also be used to monitor the physiologic signals generated at the chamber wall  125  by a low pass signal conditioner  141  which is similar to the low pass section  58  of the signal conditioner  50 . These digitized signals are then sent to the computer  34 . 
     At least one electrode pair  119  of surface electrodes  40  are also coupled to the signal generator  54  through switch  59 . Each electrode  89  and  115  are placed opposite each other on the body surface with the heart  16  in-between them. The induced field is sensed by passive electrodes  48  and conditioned by the high pass section  56  of the signal conditioner  50 . This field helps the computer  34  align or orient the passive electrodes  48  to the body for better visualization of the heart on the monitor  36 . 
     The ECG subsystem  39  accepts signals from standard ECG skin electrodes  74 . It also contains a low pass section similar to the low pass section  58  of signal conditioner  50 . In general, the passive electrode set  48  and active electrode set  52  will reside on a single catheter, however it should be recognized that other locations and geometries are suitable as well. Both basket and balloon devices are particularly well suited to this application. 
       FIG. 3  shows an electrode configuration on a balloon catheter  94  which has an inflatable balloon  96  which underlies an array or set of passive electrodes  48  typified by passive electrode  72 . These passive electrodes  48  can be organized into rows, typified by row  123 , and columns, typified by column  121 . A pair of active excitation electrodes  52  are typified by proximal electrode  92  and distal electrode  98 . The balloon catheter  94  configuration can be quite small in comparison with the basket catheter  80  configuration. This small size is desirable both for insertion into and for use in a beating heart  16 . 
       FIG. 3  also shows a movable, reference or therapy catheter system  18 . This catheter is shown lying along the interior surface  125  of the heart  16 . A pair of electrodes shown as delivery electrode  60  and reference electrode  62  are located a fixed distance apart on the catheter body  64 . This auxiliary catheter may be used to supply ablation energy to the tissue during therapy. This therapy catheter  18  may be used with either the basket catheter  60  configuration or the balloon catheter  94  configuration. 
       FIG. 4  shows an electrode configuration on a basket catheter  80 . The limbs of the basket  80 , typified by limb  82  carry multiple passive electrode sites typified by electrode  84 . A pair of active excitation electrodes are shown on the central shaft  86  of the basket  80  as indicated by excitation electrode  88 . The basket catheter  80  electrodes lie gently against the interior surface  125  of the heart  16  urged into position by the resilience of the limbs. The basket catheter  80  permits unimpeded flow of blood through the heart during the mapping procedure which is very desirable. This form of catheter also places the electrodes into contact with the heart chamber wall  125  for in-contact mapping of the physiologic potentials of the heart  16 . 
     Returning to FIG.  1  and  FIG. 2  these figures show one illustrative partitioning of system functions. In use, the signal generator  54  can generate a 4800 Hz sinusoidal signal burst on the active electrode set  52  which creates an electric field in the heart. The changing position of the chamber walls  125  and the amount of blood within the heart determines the signal strength present at the passive electrode sites  48 . For purposes of this disclosure the chamber geometry is derived from the electric field as measured at the passive electrode sites  48  which may, or may not be in contact with the walls  125  of the heart. In the case of the basket electrodes  84  which lie on the heart surface  125  the field strength is inversely proportional to the instantaneous physical wall location and the distance from the active electrodes  52  to these walls. In the case of the balloon catheter the potentials on the passive set of electrodes  72  are related to the wall location, but a set of computationally intensive field equations must be solved to ascertain the position of the wall. In general, both the basket and balloon approach can be used to generate the dynamic representation of the wall surface. 
     The computer  34  operates under the control of a stored program which implements several control functions and further displays data on a display device  36 . The principal software processes are the wall surface generation process (WSGP); the body orientation generation process (BOGP); the wall electrogram generation process (WEGP); the site electrogram generation process (SEGP); and the movable electrode location process (MELP). 
     WALL SURFACE GENERATION PROCESS 
       FIG. 5  is a flow chart describing the method used to generate the “wall surface” of the interior of the heart  16 . The step-wise processes are presented with certain physical parameters which are either known in advance by computation or are measured. This knowledge or information is shown in block  53 , block  55  and block  57 . The WSGP process begins at block  41  with the insertion of the monitoring catheter  14  in the heart  16 . This catheter  14  places an array of electrodes  44  in a heart  16  chamber. This array must have both passive measurement electrode sites  48  and active interrogation electrode sites  52  located in a known position. The process enters a measurement and display loop at block  43  where an interrogation pulse burst is generated by the signal generator  54  seen in FIG.  2 . These pulses are generated first with the current source at site  92  and the current sink at site  98  and second with the current source at site  98  and the sink at site  92  as seen in FIG.  3 . At block  45  the signal conditioner  50  uses information on the frequency and timing of the interrogation current from block  53  to demodulate the signals and analog to digital convert the signals received at the passive measurement electrodes  48 . At block  47  the information from block  55  in used. This information includes both the current strength of the interrogation pulse and the location of the interrogation source and sink electrodes. Impedance is voltage divided by current. The voltage offset caused by the location of the current source can be reduced by the two measurements of opposite polarity. This information is used to determine the impedance which the chamber and the blood contained in that chamber imposes on the field generated by the interrogation current. The knowledge from block  57  is used next. Block  49  determines how the heart chamber tissue, which has roughly three times the impedance of blood, in combination with the type of electrode array affects the field generated by the interrogation electrodes. 
     In a system as shown as the basket in  FIG. 4  the blood effects the impedance directly as the field is propagated from the interrogation electrodes to the measurement electrodes. In general, if a point current course is used within a chamber the inverse of the measured voltage is proportional to the square root of the distance from the source. With the distance from each electrode  84  to both excitation electrodes  88  computed from the measured voltage and the known location of the electrodes  84  relative to each other, the locations of each electrode  84  can be determined. 
     In a system as shown in  FIG. 3  the impedance of the field generated within the blood volume is modulated by the position of the walls  125 , with their higher impedance, with respect to the location relative to the measurement electrodes. Using this knowledge and the measurements from block  47  the distance from the interrogation electrodes to the heart chamber wall  125  is determined at a point normal to the field generated by the active interrogation electrodes  52 . 
     The passive electrodes  48  on the balloon catheter  94  can be positioned in rows  123  and columns  121  with the columns in a line from the top of the balloon  96  near active electrode  92  to the bottom of the balloon  96  near active electrode  98 . In a preferred embodiment three configurations are possible: 8 rows and 8 columns, 7 rows and 9 columns, and 6 rows and 10 columns. In each such embodiment the measurements from any row  123  are treated independently. Using the 8 row, 8 column embodiment as an example, 8 measurements of distance are taken for any selected row of electrodes, giving a total of 64 measurements. 
       FIG. 6  is a schematic drawing of the embodiment required to measure the distance  129  from the centroid  127  of the balloon  96  through the passive electrode  131  to the heart chamber wall  125 . The passive electrode  131  is one of eight electrodes on a row of electrodes  123 . Starting with electrode  131  and labeling it as electrode A, the other electrodes on the row  123  are labeled B, C, D, E, F, G and H by proceeding around the balloon  96  in a clockwise direction. The measurements of impedance “I” at these electrodes are thus labeled I A , I B , I C , I D , I E , I F , I G  and I H . To compute the distance  129  in the direction of electrode  131  the following equation is computed:
 ln( D   A )= c   0 + c   1 *ln( I   A )+ c   2 *ln( I   B )+ c   3 *ln( I   C )+ c   4 *ln( I   D )+ c   5 *ln( I   E )+ c   4 *ln( I   F )+ c   3 *ln( I   G )+ c   2 *ln(I H ) 
where D A  is the desired distance  129  and c 0  through c 5  are optimized parameters. A typical vector of these parameters is (c 0 , cl, c 2 , c 3 , c 4 , c 5 )=(3.26, −0.152, −0.124, −0.087, −0.078, −0.066).
 
     Once the distance  129  in the direction of electrode  131  is determined then the computation can be redone by shifting this direction clockwise one electrode, relabeling electrodes A through H and solving the above equation again. Once the distances for this row of electrodes  123  are determined then the next row distances are determined in the same way until the distances at all 64 electrodes are determined. 
     Returning to  FIG. 5 , with multiple wall locations in space determined by this method, a model of the chamber wall  125  shape can be created in block  51 . Various techniques for creating a shape are possible, including cubic spline fits, and best fit of an ellipsoid. The positions of the active electrodes  52  and the passive electrodes  48  relative to the heart  16  chamber walls are also determined at this point. The loop continues as the method moves back to block  43 . This loop continues at a rate fast enough to visualize the real-time wall motion of the heart chamber, at least at twenty times per second. 
     There are numerous display formats or images which can be used to present the dynamic endocardial wall surface to the physician. It appears that one of the most useful is to unfold the endocardial surface and project it onto a plane. Wire grid shapes representing a perspective view of the interior of the heart chamber are useful as well. It appears that each individual physician will develop preferences with respect to preferred output image formats. In general, different views of the endocardial surface will be available or may be used for diagnosis of arrythmia and the delivery of therapy. One distinct advantage of the present invention is that the image of the heart wall is not static or artificial. In this system the image is a measured property of the heart wall, and is displayed in motion. 
       FIG. 7  shows two separate frames of the dynamic representation of the heart wall. Wire frame  71  shows the heart at systole while wire frame  73  shows the heart at diastole. Path arrow  75  and path arrow  77  represent the dynamic cycling through several intermediate shapes between the systole and diastole representation. These views are useful as they indicate the mechanical pumping motion of the heart to the physician. 
     BODY ORIENTATION GENERATION PROCESS 
       FIG. 8  is a schematic drawing of the apparatus required to perform the body orientation generation process. It shows a patient  12  with at least one pair  119  of skin electrodes  40  attached to the body surface in a stationary position on the body and in a known configuration. These electrodes are typified by example surface electrodes  89  and  115  each of which could be an ECG electrode  74 , an RF generation current sink electrode  70 , or another electrode specifically dedicated to the BOGP. Ideally, electrode  89  and  115  are opposite one another on the body with the heart  16  directly in between them. This pair of electrodes is attached to the signal generator  54  through the switch  59  via an appropriate cable  117 . The distal end  22  of monitoring catheter  14  is situated in the heart  16  where the passive electrodes  48  can measure the signals generated across the electrode  89  and electrode  115 . 
       FIG. 9  is a flow chart describing the method used to align the wall surface representation of the WSGP to the body orientation. The process begins at step  101  where the monitoring catheter  14  with a set of passive electrodes  48  is inserted into heart  16  chamber and a pair of surface electrodes  119  are attached at a known position on the body  12 . The process begins cycling at step  102  where the signal generator  54  generates a signal across the skin electrode  89  and skin electrode  115 . At step  103  the voltage created by the signal generator  54  is measured from passive electrode  48  by the high pass section  56  of the signal conditioner  50  by using the information from block  110  which includes the frequency and timing of the field generated by the signal generator  54 . This voltage information is stored in an array “Y”. 
     At step  104  a regression analysis is performed which creates a vector which lines up with the field generated in step  103 . This regression method is the same whether a basket catheter as shown in  FIG. 4  or a balloon catheter as shown in  FIG. 3  is used. The location of each passive electrode  48  is provided to the method by block  110 . This information comes from different sources in each case however. In the case of a basket catheter  80  these three dimensional electrode locations come from the WSGP. In the case of the balloon catheter  94  these three dimensional electrode locations are known a priori. In each case they are saved in an array “X”. The regression to compute the orientation vector uses the standard regression equation for the computation of a slope:
 
 b=Σxy/Σx   2 
 
where “X” is the array of electrode locations, “Y” is the array of measured voltages and “b” is the orientation vector. If more than one pair of skin electrodes are used then an orthogonal set of orientation vectors can be created and any rotation of the monitoring catheter  14  relative to the body  12  can be detected.
 
     In step  105  the information on the location of the chamber walls  125  from the WSGP  109  can be used to create a three dimensional model of the heart  16  chamber as seen in FIG.  7 . By combining this model with the computed orientation from step  104  and the known location of the skin electrodes  108  this representation can be shown in a known orientation relative to the body in step  106 . In step  107  a specific orientation such as typical radiological orientations RAO (right anterior oblique), LAO (left anterior oblique), or AP (anterior/posterior) can be presented. By repeatedly showing this view a dynamic representation can be presented which matches the view shown on a standard fluoroscopic display. Thus such an image can be presented without the need for using ionizing radiation. 
     WALL ELECTROGRAM GENERATION PROCESS 
       FIG. 10  is a flow chart describing the wall electrogram generation process (WEGP). This process begins at block  61  when a monitoring catheter  14  with an array of passive measurement electrodes  48  is placed in a heart chamber  16  and deployed. The process enters a loop at block  63 . The frequency of the interrogation pulses generated by the signal generator  54  is provided by block  85 . With this knowledge the low pass filter section  58  of the signal conditioner  50  measures the voltage at frequencies lower than the generated interrogation pulses. Typically the highest frequency of the biopotentials is 100 Hz but can be as high as 250 Hz. 
     In the case of a basket system as seen in  FIG. 4  the measurements are contact voltages from the chamber wall  125  tissue contacting the electrodes  84 . 
     In the case of a balloon system as seen in  FIG. 3  the measurements are measurements of the field generated throughout the blood volume by the tissue on the chamber wall  125 . At step  65 , a model of the array boundary and the chamber wall  125  boundary is created from the information in block  87 . This information includes the location of the passive electrodes  48  on the array and the chamber wall  125  locations from the WSGP. 
     In the case of a basket system as seen in  FIG. 4 , the array boundary and the chamber wall  125  boundary are the same since they are in contact. The locations are determined in three-dimensional space of the sites on the chamber wall where potentials are measured. 
     In the case of the balloon system as seen in  FIG. 3 , the array boundary and the chamber wall  125  boundary are different. During step  65 , locations are generated in three-dimensional space of the sites on the chamber wall where potentials are to be determined. 
     At step  66 , the potentials are projected on to the sites on the chamber wall specified in step  65 . In the case of a basket system as seen in  FIG. 4 , the measured potentials are assigned to these sites. 
     In case of a balloon system as seen in  FIG. 3 , a three dimensional technique such as those typically used in field theory is used to generate a representation of the three dimensional field gradients in the blood volume of the heart chamber. Two examples of appropriate techniques are a spherical harmonics solution to Laplace&#39;s equation, and boundary element analysis. A more detailed description of spherical harmonics is given in the parent disclosure which is incorporated by reference herein. 
     For the boundary element method in the mapping system of the invention, the voltage is measured at the passive electrodes  48  on the probe or balloon catheter  94 . From the voltage at the electrodes on the probe and the knowledge that the probe is nonconducting, the voltage and normal current at a previously selected set of nodes on the endocardial surface  125  are determined by the boundary element method in the following manner. 
     It is known that the voltage in the blood pool between the probe and the endocardium satisfies Laplace&#39;s equation that states that the net current flow across any specific boundary is zero. To find the voltage and/or normal current on the endocardium, one must find the solution of Laplace&#39;s equation in the blood pool and calculate the values of this solution on the endocardium. Standard finite element and finite difference methods can be used to find the solution to Laplace&#39;s equation, but they have large computational overhead for generating and keeping track of a three-dimensional grid in the whole blood pool. In the mapping system of the invention, Laplace&#39;s equation is solved by the boundary element method, a specialized finite element method that permits one to restrict the calculations to the two-dimensional probe and endocardial surfaces (and not have to deal with calculations over the blood pool between these two surfaces). In order to create an accurate map of the endocardial voltage and/or normal current based on the voltage information from a limited number of electrodes on the probe, the system uses a higher-order version of the boundary element method. This system currently uses bicubic splines to represent the probe and endocardial surfaces and bilinear elements and bicubic splines to represent the voltage and the normal current on these surfaces. 
     The boundary element method consists of creating and solving a set of linear equations for the voltage and the normal current on the endocardium based on the voltage measurements at the electrodes on the probe. Each of the elements in the matrices that are involved in this set consists of two-dimensional integrals, which are calculated by numerical and analytical integration. 
     Using Laplace&#39;s equation with data given on the probe is a so-called “ill-posed” problem. For such problems, all solution procedures, including the boundary element method, are ill conditioned, that is, small errors in the measured voltage on the probe surface can result in large errors in the calculated voltage and/or normal current on the endocardium. To minimize the errors on the endocardium, options for regularization or constraints have been included in the software code. For example: the user can choose parameters that cause the code to add equations for known or expected values of the voltage and/or normal current on the endocardium. This capability is often but not exclusively used to add equations that take into account the voltage and/or normal current of the map of the previous instant(s) in time (the previous “frame(s)”). This process uses historical data from the previous frame to constrain the values subsequently computed. 
     The solution of the set of the boundary element equations and regularizing equations (if any) is normally accomplished by singular value decomposition but there is an option to solve the linear system by decomposition (Gaussian elimination) or direct or inherent methods. When singular value decomposition is used, there is an option to turn off the influence of high-frequency errors (that is, do a type of regularization) by setting various small singular values to zero, the result of which can be an increase in the accuracy of the calculated voltage and normal current on the endocardium. 
     In block  67 , a large number of points are calculated on the three-dimensional chamber surface  125 . In the case of a basket catheter as seen in  FIG. 4 , this is done through interpolation using bilinear or bicubic splines. In the case of a balloon catheter as seen in  FIG. 3 , this can be done either by using the model, such as the boundary element method or spherical harmonics to generate more points. Alternatively, bilinear or bicubic splines can be used to interpolate between a smaller number of points. 
     In block  69  a representation of the electrical potentials on the surface  125  are used to display the patterns. These types of displays include color maps, maps of iso-potential lines, maps of potential gradient lines and others. The electro-physiologic information is reconstructed on the dynamic wall surface  125 . In general the measured electrical activity is positioned by the WSGP at the exact location which gives rise to the activity. The high resolution of the system creates an enormous amount of information to display. Several techniques may be used to display this information to the physician. For example the electrogram data can be shown in false color gray-scale on a two dimensional wall surface representation. In this instance areas of equal potential areas are shown in the same color. Also a vectorized display of data can be shown on a wire grid as shown in  FIG. 11  where the distance between any two dots typified by dot pair  91  and  93  represent a fixed potential difference. The more active electrical areas show clusters of dots. In a dynamic display the dot movement highlights areas of greater electrical activity. In  FIG. 12  gradient lines typified by line  135  represent the change in potential over the chamber wall surface. Those areas with the largest change per unit area have the longest gradient lines oriented in the direction of steepest change. In  FIG. 13  iso-potential lines typified by line  95  represent equal electrical potential. In this representation the closeness of lines represents more active electrical areas. 
     SITE ELECTROGRAM GENERATION PROCESS 
       FIG. 14  is a flow chart of the site electrogram generation process (SEGP). This process is used to extract and display a time series representation of the electrical activity at a physician selected site.  FIG. 13  shows a site  97  that has been selected and a time series electrogram  99  is shown on the display device  36  along with the dynamic wall representation. Returning to  FIG. 14  this process begins at block  76  when a catheter with an array with both passive measurement electrodes  48  and active electrodes  52  is placed in a heart chamber and deployed. The process enters a loop at  78 . The inputs to the method include the wall locations from block  37 . Then the wall electrogram generator  35  provides the electrical potentials on this surface at  79 . The user will use the display  36  to determine a location of interest in block  33  which will then be marked on the display device  36  at step  81 . The voltage from this location will be collected at block  83 . This voltage will be plotted in a wave-form representation  99  in block  31 . The loop continues at this point at a rate sufficient to display all of the frequencies of such a time series electrogram  99 , at least 300 points per second. 
     The false color and vectorized display images may direct the physician to specific sites on the endocardial surface for further exploration. The system may allow the physician to “zoom” in on an area to show the electrical activity in greater detail. Also the physician may select a site on the endocardial wall  125  and display a traditional time series electrogram  99  originating at that site. 
     MOVABLE ELECTRODE LOCATION PROCESS 
       FIG. 15  is a flow-chart of the movable electrode location process (MELP). It begins at block  11  when a catheter with an array of passive measurement electrodes  48  and active electrodes  52  is placed in a heart  16  chamber and deployed. At block  13  a second catheter  18  with at least one electrode is introduced into the same chamber. The process enters a loop at block  15  where the signal generator  54  generates a carrier current between the movable location electrode  68  and an active electrode  52 . At block  17  the high pass section  56  of signal conditioner  50 , using the frequency and timing information of the location signal from block  29 , produces measured voltages from the passive measurement electrodes  48 . At block  19  the information from block  27  is used to determine the location of the electrode  68  where the location current is generated. This information includes the strength of the generated location current, the impedances of blood and tissue, the location of the active electrode  52  in use and the location of all the passive measurement electrodes  48 . One method for using this information would entail performing a three dimensional triangulation of the point source location signal using four orthogonal passive electrode  48  sites. The implementation of step  19  is the same both for the case of a basket system as seen in FIG.  3  and for the case of a balloon system as seen in FIG.  4 . In this preferred implementation, two data sets are acquired closely spaced in time such that they are effectively instantaneous relative to the speed of cardiac mechanical activity. Alternatively, the data sets could be acquired simultaneously, by driving signals at two different frequencies, and separating them electronically by well known filtering means. 
     The first data set is acquired by driving the current carrier from the location electrode  68  to a first sink or active electrode as typified by electrode  98 . This electrode is at a known location on the body of the monitoring catheter  14  relative to the array of passive electrodes  48 . The location of this first sink electrode is ideally displaced distally from the centroid  127  of the array of electrodes by at least 25 millimeters. A second data set is then acquired by driving the current from the location electrode  68  to a second active electrode  92 , located ideally at least 25 millimeters proximally from the centroid  127  of the array of electrodes. 
     The location algorithm is performed by minimizing the following equation: 
           ∑     i   =   1     n     ⁢       (       k       (         R   →     i     -       R   →     1       )     0.5       -     V     pi   1       -     b   1     -     k       (         R   →     i     -       R   →       S   1         )     0.5         )     2       +       (       k       (         R   →     i     -       R   →     1       )     0.5       -     V     pi   2       -     b   2     -     k       (         R   →     i     -       R   →       S   2         )     0.5         )     2         
 
Where n is the number of array electrodes, where k, b 1  and b 2  are fitting parameters, V pi  are the potentials measured from each i th  electrode  72 , R i  is a vector from the origin (centroid of the array of electrodes  96 ) to the i th  probe electrode  72 , R L  is the “location vector”, or three dimensional location to be solved for in the minimization, and R s1 , R s2  are the location vectors of the active sink electrodes (eg.  92  and  98 ) which are known at locations on the axis of the array of passive electrodes  48 .
 
     Additional data sets could be incorporated, following the same logic as above. Each additional squared parenthetical term requires the probe data set Vpi, another ‘b’ fitting term, and the particular active sink electrode  52  vector R s  used during the acquisition of that data set. If the sink electrode  52  is far enough away, for example using a right leg patch electrode, the fourth term in the squared expression for that data set may be deleted as R s  becomes very large. 
     It is also noted that the method does not require two data sets. The first squared expression in the above expression (requiring only data set V pi1 ) may be sufficiently accurate. 
     The non-linear least squares minimization may be performed on the above summation by any of several well-known methods. The Levenberg-Marquardt method has been used in practice to accomplish this with efficient and robust results. Nominal values for k and b are 70 and 0 respectively, when normalizing the potential values obtained as if the current source were 1 ampere. The number of parameters in the minimization for the above expression are six: k, b 1 , b 2 , and the x, y, and z coordinates of vector R L  cassuming a Cartesian coordinate system with origin at the center of the array of electrodes  96 ). 
     At step  21  a model of the heart  16  chamber wall is generated from the information provided from the WSGP  25 . Such a model can be represented on a display  36  in a manner typified in FIG.  6 . Once this surface is rendered, within this surface a second figure representing the distal end of the monitoring catheter  14  can be presented. In this way, the full three dimensional geometry of the chamber and the array catheter can be presented. 
     In step  23  this geometry is updated repeatedly to provide a dynamic view of the chamber, the monitoring catheter  18 , along with a representation of the distal end  24  of the therapy catheter  18 . If this is then combined with the electrical potentials generated by the WEGP, the therapy catheter can be moved to an electrical site of interest represented by a point in three dimensional space. 
     CALIBRATION PROCESS 
     Calibration of the system to insure that physical dimensions are accurately scaled is not a necessity for use of the system in a diagnostic or therapeutic setting. However, the availability of heart geometry in real time can permit various hemodynamic measurements to be made and displayed to the physician as well. These measurements include systolic time intervals, stroke volume and cardiac output. Calibration, where desired, requires at least two electrodes  60  and  62  a known distance apart placed along the inner-surface of the heart chamber  16 , as shown in FIG.  3 . In general the two electrode sites will each be coupled to the location signal generator  54 . The MELP of  FIG. 15  can be calibrated by scaling the calculations  50  the distance between computed locations match the known distance apart of the two electrodes  60  and  62 . Since the electrodes  60  and  62  are positioned on the chamber wall  125 , the WSGP of  FIG. 5  can be calibrated by scaling the distance measured by the WSGP in the direction of electrodes  60  and  62  to the calibrated distances measured by MELP. Finally, since the electrodes are contacting the chamber wall and providing electrograms, the WEGP of FIG.  10  and SEGP of  FIG. 14  can be calibrated to those measurements by computing the voltages at the same locations on the chamber wall  125  where electrodes  60  and  62  are located. These computed voltages can then be scaled to match the physically measured voltages from electrodes  60  and  62 . 
     THERAPY CATHETER 
       FIG. 16  is a schematic diagram of the therapy catheter system. The therapy catheter  18  has both a distal end  24  and a proximal end  26 . A handle  163  is on the proximal end  26  which allows the user to manipulate the distal end  24  and position it in the heart  16 . Referring to  FIG. 1 , this handle also permits the therapy catheter  18  to connect to the interface system  28  of the electrophysiologic apparatus  10  through the cable  32 . The location current is generated by the signal generator  54  through the switch  59  and subsequently through the wire  177  of cable  32  which is connected directly to the locator electrode  68 . The therapy catheter system also includes a therapy generator  38  which is connected to the therapy catheter handle  163  via therapy supply line  161 . The therapy supply line  161  extends through the handle  163 , through the catheter body  64 , to the therapy deployment apparatus  60  at the distal end  24  of the catheter. The locator electrode  68  is in close proximity to the therapy deployment apparatus  60  in order to determine its location within the heart  16 . 
       FIG. 17  shows an embodiment of the therapy catheter  18  using laser energy to supply the therapy. This laser catheter  165  includes the location wire  177  which connects the interface system  28  to the locator electrode  68  at the catheter&#39;s distal end  24 . In this instance the therapy supply line  161  is a fiber optic cable  167  and the therapy deployment apparatus  60  is a fiber optic terminator  169  which directs the laser energy to the site of therapy delivery. 
       FIG. 18  shows an embodiment of the therapy catheter  18  using microwave energy to supply the therapy. This microwave catheter  171  includes the location wire  177  which connects the interface system  28  to the locator electrode  68  at the catheter&#39;s distal end  24 . In this instance the therapy supply line  161  is a microwave wave guide  173  and the therapy deployment apparatus  60  is a microwave emitter  175  which directs the microwave energy to the site of therapy delivery. 
       FIG. 19  shows an embodiment of the therapy catheter  18  using a chemical to supply the therapy. This chemical deliver catheter  181  includes the location wire  177  which connects the interface system  28  to the locator electrode  68  at the catheter&#39;s distal end  24 . In this instance the therapy supply line  161  is a chemical filled lumen  183 . This lumen extends to the distal end  24  of the chemical delivery catheter  181  where a needle  185  is used to infuse the chemical into the heart chamber wall  125 . During introduction of the chemical delivery catheter  181  into the heart chamber the needle  185  is withdrawn into the catheter body through withdrawal action  187 . Once the location of the distal end  24  is determined to be at the site of interest the chemical delivery needle  165  can be deployed through the reverse of withdrawal action  187 . Potential chemicals to be used in the therapeutic delivery process include formaldehyde and alcohol. 
     Each of the therapy catheters  18  shown in FIG.  17  through  FIG. 19  as well as the radio frequency catheter shown in  FIG. 2  can be miniaturized and inserted into the coronary arterial tree. The location signal generated at locator electrode  68  can still be sensed by the passive electrodes  48  even though the signal is coming from the epicardium of the heart  16  rather than from within the heart chamber. Thus the movable electrode location process of  FIG. 15  can be used in this instance to help determine the location of the distal end  24  of the therapy catheter  18  in the coronary arterial tree and whether it is close to a site of abnormal electrical activity. Assuming that a site of ischemia will commonly be a site of abnormal electrical activity, the MELP will also enable more rapid location of potential sites for angioplasty. 
       FIG. 20  shows an embodiment of the therapy catheter  18  using balloon inflation to supply the therapy. This angioplasty catheter  191  includes the location wire  177  which connects the interface system  28  to the locator electrode  68  at the catheter&#39;s distal end  24 . In this instance the therapy supply line  161  is an inflation media supply lumen  193  and the therapy deployment apparatus  60  is an angioplasty balloon  195 . In use, a site of interest would be determined after viewing the wall electrogram generated by the WEGP of FIG.  10 . Next the angioplasty therapy catheter  191  would be positioned in the coronary arterial tree and its position determined relative to the site of interest. Next, when the distal end  24  of the angioplasty catheter  191  was at the proper location the balloon  195  would be deployed to open the artery. Finally, the electrical activity of the site would be reviewed to determine whether the underlying tissue  125  was now receiving a proper blood supply and thus was no longer electrically abnormal.